7. Contrast media II: MRI & Tutorial Flashcards
how are MRI contrast agents detected
indirectly through changing the magnetic properties of nearby water molecules
what are paramagnetic contrast agents
contain metal ions that have unpaired e-
what are the 2 types of paramagnetic contrast agents
gadolinium based
non gadolinium
what are the 2 paramagnetic metal ions
gadolinium and manganese
what do paramagnetic metal ions do to the T1 and T2 proton relaxation times
efficiently reduce both
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
what aspect of proton relaxation time does T1 agents reduce
longitudinal
what aspect of proton relaxation time does T2 agents reduce
transverse
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
what does it mean when an ion is chelated
bonds formed around metal ion stabilise it and prevents large amount from accumulating in body
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
classificaiton of T1 or 2 depends on what
on the relative relaxation time is greater for T1/2
how many unpaired e- does gadolinium have
7
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
gadolinium ions are hydrolysed at what pH and what does it produce
hydrolysed at physiological pH to produce insoluble Gd(OH)3
what does chelation do to renal elimination and distribution
enhances renal elimination and limits distribution in the extravascular space
what are the 4 aspect in the classification of GBCAs
shape
ionicity
biodistribution
risk of nephrogenic systemic fibrosis
is PK affected by the chemical structure of GBCAs
no
what does tight chelation prevent
prevents cellular uptake of gadolinium ion
what are the 2 shapes of GBCA
macrocyclic and linear
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
what is the characteristics of linear shaped GBCA in terms of rigidity, stability and protection
flexible
open chains
fold and unfold easily
what are the 2 forms of biodistribution for GBCA
nonspecific agents
specific agents
what are non specific agents
no specific interaction with a particular cell type
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
no
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
5
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
