MRI contrast media

1. MRI Contrast Agents
Sultan Rashid Alsalti
Sultan.alsalti@gmail.com
MSc in Magnetic Resonance Imaging

2. Objectives
• Definitions.
• Justification.
• Types Of MRI Contrast Agents.
• Requirement of an MRI contrast agent.
• Gadolinium.
• Gadolinium Dose and administration.
• Contraindications of gadolinium
• Biodistribution of GA-based MR contrast agents .

3. MRI contrast
First

4. Definition
MRI stands for Magnetic resonance Imaging, MRI is one
of the most advanced means of looking into the living
human body.
Strong Magnet Radiofrequency Spinning the H2O
protons

5. The images we see is the hydrogen proton from water or fat
effected by magnet has been proceed to finalized it as an image
Definition

6. • Contrast agents are pharmaceuticals that increase the information
content of diagnostic images. They serve to improve the sensitivity
and specificity of diagnostic images by altering the intrinsic properties
of tissues
Definition

7. Brief History:
• In 1981 the first contrast-enhanced human MRI study was report
using ferric chloride as the contrast agent in the gastrointestinal (GI)
tracted.
• In 1984 Carr et al first proved the use of a gadolinium compound as
a diagnostic intravascular MRI contrast agent.
Definition

8. Contrast agents are Paramagnetic
pharmaceuticals are known to shorten the
T1 and relaxation times of the adjoining
hydrogen nuclei.
Definition

9. Definition
Contrast agent effect on T1 Image

10. Justification
T2 T1
T1 & T2 relaxation time of
tissue changes by disease
process
Difficult to separate
abnormal tissue from
Adjacent normal tissue

11. Justification
• Identifying and improve abnormalities detections.
• Increase sensitivity to extent of the disease.
• Increase differentiation between normal tissue and abnormal tissue.
• Does the lesion contains solid, cystic, viable and /or necrotic tissue.
• Identify the lesion weather it’s hypervascular or hypovascular.
• Characterised and identify if the lesion malignancy or benign.
• Perfusion characterization.

12. Types of contrast agent
Paramagnetic
dysprosium (Dy3+)
gadolinium (Gd3+)
manganese (Mn2+)
Ferromagnetic
Iron(Fe56+)
Nickel (Ni58+)
cobalt (Co59)
weakly influence a magnetic field Large magnetic susceptibility

13. Requirement of an
MRI Contrast Agents
It’s ability to influence the MRI parameters for image contrast.
visible enhancement in minimum dose to reduce potential toxicity.
Should reflect the change in disease, and biological function .
Remain in tissue for sufficient time .
Lack to all reactivity within the body.
Chemically stable with law viscosity.
Low cost.
Requirements of an MRI Contrast Agents

14. Gadolinium
Gd
Periodic Table
64
Gd
Gadolinium

15. Gadolinium
• Rare earth metal of lanthide
• Atomic number 64
• Can be Combined with chelates to prevent toxicity by rapid and
total exceration.
• Plays a role in both T1 and (slight effect in T2 relaxation).
• Increased brightness in T1, This T1 effect of Gadolinium are used
more in clinical purposes.
• Gadolinium leads to T2 reduction and decreased signal on T2 image
• Has 7 unpaired electrons in its 4f shell, the most of any
element in the periodic table

16. Gadolinium
(chelates)
• Gadolinium chelating agent which modifies the distribution of
gadolinium within the body to overcome its toxicity while maintaining
its contrast properties.
• Chelates is a safe ‘chemical wrapper’
• Decreases the interactions with the human body.
• Increases the speed of elimination from the body.
• Determines the biodistribution into the extracellular space and
elimination pathway.

17. Gadolinium
(chelates)

18. Gadolinium
(chelates)
Chelator
Ionic
Macrocyclic
Linear
Non-Ionic
Macrocyclic
Linear
Behazdi et al (2018)-Reactions with Ionic > non ionic

19. N N N
-O2C
-O2C
-
CO2
Gd 3+
Elongated organic
molecular ligand that
tightly wraps around the ion
Gd3+
-
CO2
-
CO2
Gadopentatate dimeglumine
Linear Chelator

20. N N
N N
Gd 3+
-O2C
2
-O C
-
CO2
2
CO -
Cage like
structure
Gd3+
Macrocyclic Chelator
Gadoterate

21. Gadolinium
On going studies: gadolinium deposition
• Various studies have shown evidence of Gd deposition in the
paediatric brain irrespective if renal function
• Diversity of results
• Some suggestions that MRI is not sensitive enough to demonstrate
T1 hyperintensities associated with macrocyclic agents
• Animal studies found that deposition occurs in three forms- soluble
small molecules, soluble macromolecules and insoluble gadolinium
(Frentzel et al, 2017)

22. Gadolinium
On going studies: gadolinium deposition
• Kanda et al (2014) first reported evidence of high signal intensity in
the dentate nucleus and globus pallidus.
• Kanda et al (2015) found that it was associated with past linear
chelate administration but not with macrocyclic administration.

23. Gadolinium dose and administration
(Dotarem)
For adult and paediatric patients (including term neonates), the
recommended dose of DOTAREM is 0.2 mL/kg (0.1 mmol/kg) body
weight.

24. Gadolinium dose and administration
(Dotarem)
• administered as an intravenous bolus injection, manually or by power
injector
To ensure complete injection of the contrast, injection may be followed by normal saline flush.
flow rate of
approximately 2
mL/second for
adults and 1-2
mL/second for
paediatric patients

25. Contraindications
• The reaction is rare in gadolinium (1:1000)
• Lower does for people under 50 KG
Anaphylactic
reactions
• contrast passed cross the human placenta and into the fetus
when given in clinical dose ranges.
• MR contrast agents should not be routinely provided to
pregnant patients
Pregnancy
• Before injecting contrast renal function test needed.
• Nephrogenic systemic fibrosis.
• don’t inject if (eGFR of <30 ml/min/m2)
Renal
impairment
• If contrast to be giving. Stop breast feeding for 24 hours.
• Mother asked to express and discard breast milk from both breasts
during that period of 24 hours
Breast feeding

26. Contraindications
Check before inject
• A prior drug hypersensitivity reaction
• Prior reaction to a Gadolinium.
• Asthma requiring medical treatment ?Premedication (prednisolone)
• If increased risk consider alternative test and a different contrast
agent should be considered
Keep all patients that have received a dose and have the risk of
reaction in the department for 30 minutes.
Risk of Immediate Adverse reaction

27. Acute
Chemotoxic
Allergic/hypersensitivity
Within 60
minutes
Late
1 hour – 1 week
Skin reactions not
associated with GBCA
Very Late
> 1 week
Nephrogenic Systemic
Fibrosis
Types of adverse reactions
Contraindications

28. Contraindications
Nephrogenic systemic fibrosis
• NSF affects patients with advanced or acute renal insufficiency
• Scleroderma like skin lesions
• Flexion contractures of joints
• Fibrosis may also affect liver, lung, heart, muscles

29. Contraindication
High NSF Risk
Chelator
Ionic
Macrocyclic
Linear
Non-Ionic
Macrocyclic
Linear
Behazdi et al (2018)-Reactions with Ionic > non ionic

30. Contraindication
• Recommendation from European Medicines Agency,
Macrocyclic Linear
Dotarem Prohance Gadovist Primovist
Safety profile
not
established<18
Magnevist Multihance Omniscan Optimark
      
Low NSF
RISK
High NSF
RISK

31. Contraindication
RFT
eGFR
always do

32. Biodistribution of GA-based MR contrast agent .

33. In Summary
• Spread NSF condition awareness
• ‘Gadolinium deposition disease’
• Administer with caution
• Be aware of any risk factors
• Lowest dose possible
• Always ask Radiologist review of pre-contrast images.
• Use of macrocyclic agents
• Review of protocols

34. Thank you
Question

35. References
• Behzadi, AH., Zhao, Y., Farooq, Z., Prince, MR., (2018) Immediate Allergic
Reactions to Gadolinium – Based Contrast Agents: A Systematic Review and
Meta-Analysis, Radiology, 286 : 471
• Grobner, T (2006) Gadolinium – a specific trigger for the development of
nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?
Nephrology Dialysis Transplantation, 21(4) : 1104-1108
• Markmann, P., Skov, L., Rossen, K., Dupont, A., Damholt, MB., Heaf, JG.,
Thomsen, H. (2006) Nephrogenic Systemic Fibrosis: Suspected Causative Role
of Gadodiamide Used for Contrast-Enhanced Magnetic Resonance Imaging,
Journal of American Society of Nephrology, 17 : 2359-2362
• Nardone, B., Saddleton, E., Laumann E et al (2014) Pediatric Nephreogenic
Systemic Fibrosis is rarely reported: A RADAR Report, Paediatric Radiology;
44:173-180

36. • Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., Takenaka, D. (2014) High Signal Intensity in
Dentate Nucleus on Unenhanced T1 Weighted Images : relationship with increasing
cumulative dose of a gadolinium-based contrast material, 270 (3) : 834-841
• Kanda, T., Osawa, M., Oba, H., Toyoda, K., Haruyama, T., Takeshita, K., Furui, S. (2014)
High Signal Intensity in Dentate Nucleus on Unenhanced T1 Weighted Images :
Association with Linear versus Macrocyclic Gadolinium Chelate Administration,
Radiology, 275 (3) : 803-809
• Ramalho, J; Castillo, M; AlObaidy, M; Nunes, RH; Ramalho, M; Dale, BM.; Semelka, RC.
(2015) High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-
weighted MR images: evaluation of two linear gadolinium-based contrast agents.
Radiology, 276, 836-844.
• Perrotta, G., Metens, T., Absil, J., Lemort, M., Manto, M (2017) Absence of clinical
cerebellar syndrome after serial injectiosn of more than 20 doses of gadoterate, a
macrocyclic GBCA: a monocenter retrospective study, Journal of Neurology, 264 : 2277-
2283
References

37. • Frenzel et al (2017) Quamntification and assessment of the chemical
form of residual gadolinium in the brain after repeated
administration of gadolinium based contrast agents : comparative
study in rats. Investigative Radiology, 52 : 255- 264
References