7. Contrast media II: MRI & Tutorial Flashcards by J Y

how are MRI contrast agents detected

indirectly through changing the magnetic properties of nearby water molecules

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what are paramagnetic contrast agents

contain metal ions that have unpaired e-

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what are the 2 types of paramagnetic contrast agents

gadolinium based

non gadolinium

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what are the 2 paramagnetic metal ions

gadolinium and manganese

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what do paramagnetic metal ions do to the T1 and T2 proton relaxation times

efficiently reduce both

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what is relaxation times

relaxation time is the time taken for protons in water molecules to go back to a relaxed state from excited state

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what aspect of proton relaxation time does T1 agents reduce

longitudinal

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what aspect of proton relaxation time does T2 agents reduce

transverse

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why cant the paramagnetic metal ions be used as contrast agents in their ionic from

as a result what must be done to them

toxic and undesirable distribution and accumulation in the body

must be chelated into a complex

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what does it mean when an ion is chelated

bonds formed around metal ion stabilise it and prevents large amount from accumulating in body

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what is the relationship between T1 and T2 reduction

Any contrast that reduces T1 will also reduce T2 but contrast that is T2 reducing wont necessarily decrease T1

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classificaiton of T1 or 2 depends on what

on the relative relaxation time is greater for T1/2

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how many unpaired e- does gadolinium have

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what does it mean when we say that gadolinium ions are cytotoxic

blocks voltage gated calcium channels at very low conc and inhibits certain enzymes

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gadolinium ions are hydrolysed at what pH and what does it produce

hydrolysed at physiological pH to produce insoluble Gd(OH)3

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what does chelation do to renal elimination and distribution

enhances renal elimination and limits distribution in the extravascular space

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what are the 4 aspect in the classification of GBCAs

shape
ionicity
biodistribution
risk of nephrogenic systemic fibrosis

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is PK affected by the chemical structure of GBCAs

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what does tight chelation prevent

prevents cellular uptake of gadolinium ion

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what are the 2 shapes of GBCA

macrocyclic and linear

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what is the characteristics of macrocyclic shaped GBCA in terms of rigidity, stability, binding to Gd and protection

rigid
more stable
stronger binding to gadolinium
better protection

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what is the characteristics of linear shaped GBCA in terms of rigidity, stability and protection

flexible
open chains
fold and unfold easily

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what are the 2 forms of biodistribution for GBCA

nonspecific agents

specific agents

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what are non specific agents

no specific interaction with a particular cell type

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what are specific agents

targeted agents

what are the 2 types of non specific agents

extracellular fluid agents | blood pool agents or intravascular agents

what is the ECF agents characteristics in terms of MW, movement from intravascular space and excretion route

low MW complexes equilibrate rapidly between intravascular and interstitial space excreted renally

what is the blood pool agents characteristics in terms of MW, movement from intravascular space and excretion route

high MW complexes stays within the intravascular space slowly excreted via the kidneys and or the liver

ECF agents diffuse from blood to where and what effect does this have on acquisition time

rapidly from blood to Extracellular space, limits acquisition time to 1-3mins

how is ECF agents excreted

renally

what is the elimination half life for ECF agents in normal renal function

1.5 hrs

what is the elimination half life for renally impaired people

up to 34hrs

in patients with normal BBB does accumulation occur

limited permeation

in patients with diseased BBB does accumulation occur

accumulation may appear

what are the 2 types of ECF agents

ionic and non ionic

wjat is the size of blood pool agents in comparison to ECF agents

larger in size

what does blood pool agents do to the diffusion between fluid compartments

prevents diffusion from blood to interstitial fluid remains in intravascular space

does blood pool agents need metabolism and if yes what for

yes requires metabolism of the macromolecules for renal excretion

the fact that blood pool agents need metabolism for renal excretion has what effect on the plasma conc and image acquisition time

maintains conc in plasma stable over 1h image acquisition time increased to 1hr in comparison to ECF

what does blood pool agents do in terms of time it remains and where it remains

remains for longer time in intravascular space

why is blood pool agents advantageous over ECF agents

longer image acquisition time that allows higher resolution and better quality angiograms

what does blood pool agents allow in terms of measurement

allows tissue blood volume and perfusion to be measured

what does blood pool agents allow in terms of enhancement

allows enhancement in both arteries and veins

what are the 2 further categorisations for blood pool agents

albumin binding gadolinium complexes polymeric gadolinium complexes

what is the binding like for albumin binding complexes and is the reversible

extensive binding to plasma proteins like albumin reversible

where is albumin binding complexes confied

intravascularly

what is the relative retention time of albumin binding complexes

longer retention within the blood

how much of the albumin binding complexes reach the ECF

only a small amount

can albumin binding complexes be used interchangeably with ECF agents

what are the 2 phases of tissue specific liver agents

extracellular phase and delayed hepatocyte uptake and biliary excretion

what does the extracellular phase of tissue specific liver agents allow

imaging of vasculature

what does the delayed hepatocyte uptake phase of tissue specific liver agents allow

evaluation of hepatic tissues with altered functions

what are the 2 elimination pathways for tissue specific agents

hepatobiliary | renal

what are 2 examples of tissue specific agents

multihance and eovist/primovist

what is the protein binding, metabolism and elimination of multihance like

no significant protein binding and metabolism elimination via kidneys

what is multohance a substrate for - 2 transporters

OATP1 and cMOAT

renal impairment does what to multihance

prolongs elimination of multihance

what effect does hepatic impairment have on the PK of multihance

little impact

what is multihance in terms of cMOAT drugs

competitive inhibitors of cMOAT drugs

what is multihance in terms of heart electrical activity

QT prolongation, distorts the hearts electrical activity

what are the 3 aspects that multihance and primovist differ in

uptake by hepatocytes acquisition times for hepatobiliary phase compensatory elimination

how does multihance and primovist differ in terms of uptake by hepatocytes

multihance has 97% renal elimination | primovist has 50/50 biliary and renal excretion

how does multihance and primovist differ in terms of acquisition time for the hepatobiliary phase

``` multihance = 1-3 hrs after administration (~2hrs) primovist = 10-120min after administration (~20min) ```

compared to ICM what is gadoliniums rate of adverse reactions

lower rate

what is the osmolality of MRI contrast agents in relation to plasma

hyperosmolar

what is the viscosity of MRI CM compared to ICM

lower

what is the injection volume like for MRI CM compared to ICM

lower injection volumes to decrease osmotic load

does osmolality, ionicity and viscosity of GBCAs play significant role in tolerability and safety in what scenario does this answer apply

no if at standard dose and volume

what variable indicates how tightly the gadolinium is bound/chelated

equilibrium constant

what is the equilibrium constant of gadolinium presented on in terms of scale and what does larger values mean for the binding what are lower values associated with

log scale larger values = tighter binding lower values associated with higher rate of NSF due to accumulation of Gd in tissues

what are the acute adverse reactions to GBCAs

similar to ICM

what are the renal adverse effects for GBCAs in terms of the CI-AKI at usual MRI doses compared to ICM

very low risk

what are the 4 reasons for thinking that GBCAs are associated with lower renal toxicity

low doses, volumes, viscosity and injection rates

GBCAs were thought to be less renal toxic until what was reported

Once thought GBCA associated with less renal toxicity until NSF was reported

what is nephrogenic systemic fibrosis

fibrosing disorder

what are the 4 most common manifestations of nephrogenic systemic fibrosis

thickening and hardening of skin muscle weakness bone pain joint contractures

is nephrogenic systemic fibrosis reversible and can it be treated

irreversible and no treatment available

in what patients has nephrogenic systemic fibrosis be reported

patients with impaired renal function

what is nephrogenic systemic fibrosis believed to begin with

displacement of Gd ions from its chelate by another metallic ion

what is transmetallation reaction and what is the chemical equation

displacement of Gd ions from its chelate by another metallic ion metal ion + Gd chelate metal chelate + Gd3+

why is incidence of NSF difficult to define

NSF symptoms can develop many years after exposure

what are 2 high NSF risk contrasts

omniscan | magnevist

what are 2 medium NSF risk contrasts

primovist | multihance

what are 2 low NSF risk contrasts

dotarem | gadovist

what are the patient related risk factors for NSF

severe renal dysfunction

what are 2 contrast related risk factors for NSF

type - linear agents | repeated injections

what is the importance of renal functions in terms of GBCA dissociation and accumulation

patients with poor renal function have reduced GBCA excretion so GBCA remain in the body for a longer time which increases the risk of gadolinium dissociating and accumulating in body

gadolinium deposition occurs in certain brain regions and are dependent on what and independent of what 2 factors

dose dependent independent of renal function and BBB integrity

what are the EMA recommendations for GBCAs in terms of shape

linear gadolinium agents release Gd to greater extent than macrocyclic

what are the 3 medsafe GBCAs reccomendations in terms of usage, dose and shape

limit use of GBCAs where possible use the approved dose where possible macrocyclic agents preferred over linear agents

what gadolinium agents can prolong coagulation time

ionic and non ionic

ionic and non ionic Gd agents can potentiate effects of what 2 medicines

anticoagulant antiplatelet fibrinolytic

what lab test can GBCA interfere with

calcium level test

can GBCA cross the placenta and if needed to be used what type should be used

yes macrocyclic

half life of GBCA can be what in paeds

can be prolonged

why is half life of GBCA prolonged in premature infants

lower GFR and renal clearance rate than older children and adults

what is the increased risk of GBCA for paeds

may have increased risk of increased exposure to free Gd

what are the 4 recommendations for paeds in terms of GBCAs

Gd based CM should not be first choice macrocyclic agents should be used renal function must be assessed multiple dose should be avoided

GFR < what means GBCA shouldnt be used

if its <30mL/min/1.73.^2

what are manganese based contrast agents

paramagnetic

how many unpaired e- does manganese based CM have

what are natural oral contrast agents and why are they CM

fruit juice - blueberry and pineapple as they contain high level of manganese

what is US contrast

gas containing microbubbles or microspheres for injection

7. Contrast media II: MRI & Tutorial Flashcards

(103 cards)