Effects of Anesthesia on Pediatric

Brain MR Imaging

Julie Harreld, MD

St. Jude Childrens Research Hospital

Memphis, TN

Anesthesia and MRI

Pediatric MRI highly dependent on anesthesia All young children (

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

Miller RD EL, Fleisher LA, Wiener-Kronish JP, Young WL. Miller's

Anesthesia. Vol I. 7th Edition ed: Elsevier, Inc. ; 2010.

Most decrease cerebral metabolism

Decrease CBF Vasoconstriction Inhibition of NO-

mediated vasodilatation

Secondary to decrease in cerebral metabolism

Depress EEG response (cortical activity)

Prototype: propofol

Inhalational Anesthetics

Miller RD EL, Fleisher LA, Wiener-Kronish JP, Young WL.

Miller's Anesthesia. Vol I. 7th Edition ed: Elsevier, Inc. ; 2010.

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)

Examples: Sevoflurane Desflurane Isoflurane Enflurane Halothane

Perfusion effects differ

DSC perfusion MRI in 55 childrenCBF did not follow expected age-related curve in anesthetized patients

Age-related trends in CBF, CBV differed between anesthesia types

Harreld et al, Neuroradiology, (in press)

Anesthesia-induced changes in perfusion could be mistakenly

attributed to pathologyEx: comparison or longitudinal analysis of global perfusion changes

due to therapy or disease

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?

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.

Scan 1. Increased signal in

sulci.

CSF Hyperintensity on FLAIR

Artifact or Disease?

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).

Scan 2. Increased signal

in sulci has decreased.

fMRI

StimulusCBF

Cerebral

Metabolism

Relatively less

extraction O2, so

MORE O2-Hb

(paramagnetic), in that

volume of blood

Signal in activated

volume ( %

paramagnetic Deoxy-

Hb, which signal )

BOLD EFFECT

Neurovascular coupling Neurons Astrocytes

Coupling of post-synaptic activity to metabolism and vascular response (CBF)

Vessels

Neuron

Anesthetic Actions on Neurovascular

Coupling

Neuronal

activityStimulus

CBF

Metabolism

Signal1

3 5

6

72

4

8

Neuronal ActivityGABA-ergic:

Propofol

Pentobarbital

Isoflurane

2 LatencyPropofol

Isoflurane (dose-

related)

ketamine, fentanyl

1 Optimal Stimulus

FrequencyIsoflurane

3

Glutamatergic

transmission Ketamine,

pentobarbital

4

CBFpropofol,fentanyl,

diazepam,midazolam

isoflurane,sevoflurane

5

Cerebral Metabolismpropofol,fentanyl,

diazepam,midazolam

isoflurane,sevoflurane

halothane

6

CBF-Metabolic

Couplingvolatile anesthetics

(thanes)

7

Spatial Coordinationisoflurane

8

Buxton 2010; Franceschini 2010; Magistretti 2006, 2009; Masamoto 2012;

Qiu 2008; Szabo 2009; Veselis 2005

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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