Effects of Anesthesia on Pediatric
Brain MR Imaging
Julie Harreld, MD
St. Jude Children’s Research Hospital
Memphis, TN
Anesthesia and MRI
• Pediatric MRI highly dependent on anesthesia
– All young children (<6 years)
– Some older children (behavioral, respiratory
issues, apprehension)
– Orbit imaging
– ~50% of MRI in our pediatric practice
Anesthetic Physiology
• Anesthesia has known effects on
– Cerebral blood flow (CBF) and cerebral blood
volume (CBV)
– Vasoreactivity and vessel caliber
– Cerebral metabolism
– Normal neurovascular coupling
Physiologic & Anatomic MR Imaging
• Anesthetic effects may manifest in many ways on MRI
– Cerebral blood flow (CBF) and cerebral blood volume (CBV)
• Perfusion MRI
– Vasoreactivity and vessel caliber
• Perfusion MRI
• Susceptibility-weighted imaging
• fMRI
– Cerebral metabolism
• Perfusion MRI
• fMRI
– Neurovascular coupling
• fMRI
– CSF Artifact
• FLAIR imaging
Intravenous Anesthetics/Analgesics
• Examples:
–
–
–
–
–
–
–
–
Propofol
Etomidate
Thiopental
Midazolam
Diazepam
Fentanyl
Dexmetomidine
Sufentanil
• Most decrease cerebral
metabolism
• Decrease CBF
– Vasoconstriction
– Inhibition of NOmediated vasodilatation
– Secondary to decrease in
cerebral metabolism
• Depress EEG response
(cortical activity)
– Prototype: propofol
Miller RD EL, Fleisher LA, Wiener-Kronish JP, Young WL. Miller's
Anesthesia. Vol I. 7th Edition ed: Elsevier, Inc. ; 2010.
Inhalational Anesthetics
• Examples:
–
–
–
–
–
Sevoflurane
Desflurane
Isoflurane
Enflurane
Halothane
• Increase cerebral metabolism
• Effect on CBF varies with time
and dose
– Initial increase, then decrease
– Direct vasodilators (increases
with dose), independent of
CMR
• Decoupling of CBF and
cerebral metabolism
• Frequently used with another
agent (ex: propofol)
Miller RD EL, Fleisher LA, Wiener-Kronish JP, Young WL.
Miller's Anesthesia. Vol I. 7th Edition ed: Elsevier, Inc. ; 2010.
Perfusion effects differ
• DSC perfusion MRI in 55 children
•CBF did not follow expected agerelated curve in anesthetized patients
•Age-related trends in CBF, CBV differed
between anesthesia types
•Anesthesia-induced changes in
perfusion could be mistakenly
attributed to pathology
•Ex: comparison or longitudinal
analysis of global perfusion changes
due to therapy or disease
Harreld et al, Neuroradiology, (in press)
What about ratios?
• Ratio-based measures of CBV, CBF used to grade
tumors, distinguish from radiation necrosis
– Tumor:normal brain
• rCBV>1.98, rCBF>1.25 = high-grade glioma (Hayyemez et al, 2005)
– Lesion:normal brain
• rCBV > 2.1 =recurrence (vs. radiation necrosis) (Mitsuya et al, 2010)
• rCBV>1.75 predicts progression (Law et al, 2006 & 2008)
rCBV > 2.1 (tumor)
Ratios
• Tumor: normal brain
ratio may change with
anesthesia
– Vasoreactivity of tumor
neovascularity likely
differs from normal
vessels
• GM:WM ratio
– Generally accepted that CBF and
GM/WM ratios decrease with
age (Huisman 2004; Biagi 2007; Ogawa 1989)
– Trends altered with anesthesia
Adapted from Cenic et al, 2005
Awwad, Harreld et al, ISMRM 2013
Vessel conspicuity on SWI
• Veins appear dark on SWI due to deoxyhemoglobin
• Increasing CBF, ETCO2 decreases venous deoxy-Hb (more
oxygenated venous blood), decreasing venous conspicuity
[BOLD effect] (Sedlacik et al, 2010)
– Could lead to underestimation of extent of vascular lesions (ex: AVM)
– Could impact attempts to stage tumors with SWI (Hori et al, 2010)
Sevoflurane.
CBF=78.9, CBV=10.5, ETCO2 =51
Propofol.
CBF=40.9, CBV=5.65, ETCO2 =37.25
CSF Artifact on FLAIR
• Artifactual CSF signal intensity in sulci and cisterns can mimic
or obscure leptomeningeal disease
• Attributed variably to
– Anesthetic agents
– Supplemental O2 administered with anesthesia
• Attributed to T1 effects
– Recent study found effect of anesthetic agent to be dominant (Harreld et
al, ASNR 2012)
Variable sulcal signal intensity in patients without leptomeningeal disease.
CSF Hyperintensity on FLAIR–
Artifact or Disease?
Scan 1. Increased signal in
sulci.
6yo M with L frontoparietal skull Ewing sarcoma. Post-contrast FLAIR
image (left) [3T; TR10000, TE 108, TI 2604.7, 20 ch head coil] shows
diffusely increased signal in sulci.
CSF Hyperintensity on FLAIR–
Artifact or Disease?
Scan 2. Increased signal
in sulci has decreased.
Same patient 3.5 months later, no intervening treatment. Same magnet and imaging
parameters. Post-contrast FLAIR image (left) shows decrease in increased signal in sulci.
Only difference: Sevoflurane GA on Scan 1 (see oral airway device) and propofol on Scan 2
(see NC).
fMRI
CBF
Stimulus
Neuron
Cerebral
Metabolism
Relatively less
extraction O2, so
MORE O2-Hb
(paramagnetic), in that
volume of blood
Signal in activated
volume ( %
paramagnetic DeoxyHb, which signal )
BOLD EFFECT
• Neurovascular coupling
– Neurons
– Astrocytes
• Coupling of post-synaptic activity to metabolism and
vascular response (CBF)
– Vessels
Anesthetic Actions on Neurovascular
Coupling
5
3
1
2
Stimulus
Neuronal
activity
CBF
8
7
4
Signal
Metabolism
6
1 Optimal Stimulus
Frequency
Isoflurane
2 Latency
Propofol
Isoflurane (doserelated)
∆ ketamine, fentanyl
3 Neuronal Activity
GABA-ergic:
Propofol
Pentobarbital
Isoflurane
4 Glutamatergic
transmission
Ketamine,
pentobarbital
Buxton 2010; Franceschini 2010; Magistretti 2006, 2009; Masamoto 2012;
Qiu 2008; Szabo 2009; Veselis 2005
5 CBF
propofol,fentanyl,
diazepam,midazolam
isoflurane,sevoflurane
7 CBF-Metabolic
Coupling
volatile anesthetics
(thanes)
6 Cerebral Metabolism 8 Spatial Coordination
propofol,fentanyl,
diazepam,midazolam
isoflurane,sevoflurane
halothane
isoflurane
fMRI
• Propofol (and other IV anesthetics) decrease
cortical activity and CBF
– CBF response (coupling)
• preserved at sedative, but not hypnotic, concentrations
(Veselis 2005)
– Latency
• increases with propofol (Franceshini 2010)
• Volatile anesthetics (e.g. sevoflurane, isoflurane)
– Disrupt CBF-Metabolic coupling
– May affect optimal stimulus frequency
– May alter spatial coordination of activation and BOLD
signal
Conclusion
• Significant challenge in pediatric neuroimaging
• Be cautious when interpreting quantitative MR imaging
in anesthetized children
• Be aware of effects on anatomic images (FLAIR, SWI)
• Possible solutions
–
–
–
–
Standardized anesthesia
New “normals” for CBF, CBV under anesthesia
Consideration in statistical analysis
More research characterizing effects in children
• More sensitive than adults to vasodilatory effects sevoflurane
• Data in adults may not apply to children
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