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Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters
Ryne A. Didier1,2, Anush Sridharan1, Kendall Lawrence1, Juan S. Martin-Saavedra1, Marcus G. Davey1,2, Beverly G.
Coleman1,2, and Alan W. Flake1,2
1The Children’s Hospital of Philadelphia
2Perelman School of Medicine, University of Pennsylvania
Disclosures
• No financial disclosures
Introduction
1. Meairs, S., & Kern, R. Front Neurol Neurosci.2015;36:57-70.
• Contrast-enhanced ultrasound (CEUS)
Evaluation of fetal Brain perfusion
Sagittal image demonstrating enhancement of the pericallosalartery of a fetal brain
Objectives
•Use of CEUS to:• Evaluate brain perfusion and cerebral blood flow with
partial amniotic fluid carbon INSUFFLATION.•Correlate brain perfusion parameters with
hemodynamics and acid-base status
Materials & Methods - Surgery
POD 2-3Experimental surgery,
continuous monitoring
GA 101-106Fetal carotid artery catheter
Study period
Materials & Methods - Subjects
N= 4
Age m
atche
d
General anesthesia + CO2 insufflation
General anesthesia only
End of Study
End of Study
GA = 105±1
N= 3
Arterial blood gases + CEUS examination of the fetal brain
Materials & Methods- CEUS
GE Loqiq E9
GE C2-9
transducer
0.1-0.3mLContrastinjection
Materials & Methods – CEUS Variables
Time (s)
Ech
o-P
ow
er (
a.u
.)
Transit Time
Rise Time
Time to Peak
Fall Time
Results – Perfusion vs. pCO2C
on
tro
lIN
SUFF
LATE
D
Co
ntr
ol
PA
CI
Co
ntr
ol
PA
CI
Co
ntr
ol
PA
CI
Co
ntr
ol
PA
CI0
5
1 0
1 5
2 0
2 5
Se
co
nd
s
T T P R T F T T T
**
*
** p < 0.05
Time (s)
0 6 0 1 2 0 1 8 0 2 4 0
7 .0
7 .1
7 .2
7 .3
7 .4
A n e s th e s ia t im e
(m in u te s )
pH
*
0 6 0 1 2 0 1 8 0 2 4 0
4 0
6 0
8 0
1 0 0
1 2 0
A n e s th e s ia t im e
(m in u te s )
Art
eri
al
CO
2(m
m H
g)
*
Results – ↑CO2 and ↓pH
0 6 0 1 2 0 1 8 0 2 4 0
1 0 0
1 5 0
2 0 0
A n e s th e s ia t im e
(m in u te s )
He
art
ra
te (
bp
m) p = 0 .9 7 , P A C I v s . C o n tro l
C o n tro l
P A C I
0 6 0 1 2 0 1 8 0 2 4 0
0
1 0
2 0
3 0
4 0
A n e s th e s ia t im e
(m in u te s )
Art
eri
al
pO
2(m
mH
g)
p = 0 .7 8 , P A C I v s . C o n tro l
C o n tro l
P A C I
Results – Stable pO2 and Heart Rate
Results – Perfusion vs. pCO2
0 5 0 1 0 0 1 5 0
0
1 0
2 0
3 0
p C O 2 (m m H g )
Tim
e t
o p
ea
k (
s)
r2
= 0 .6 1
0 5 0 1 0 0 1 5 0
0
4
8
1 2
p C O 2 (m m H g )
r2= 0 .6 7
Ris
e T
ime
(s
)
0 5 0 1 0 0 1 5 0
0
5
1 0
1 5
2 0
2 5
p C O 2 (m m H g )
Fa
ll
Tim
e (
s) r
2= 0 .6 5
0 5 0 1 0 0 1 5 0
0
1 0
2 0
3 0
4 0
p C O 2 (m m H g )
r2
= 0 .6 8
Tra
ns
it t
ime
(s
)
p < 0.01
p < 0.01
p < 0.01
p < 0.01
𝑇𝑟𝑎𝑛𝑠𝑖𝑡 𝑇𝑖𝑚𝑒 =𝐶𝑒𝑟𝑒𝑏𝑟𝑎𝑙 𝐵𝑙𝑜𝑜𝑑 𝑉𝑜𝑙𝑢𝑚𝑒
𝐶𝑒𝑟𝑒𝑏𝑟𝑎𝑙 𝐵𝑙𝑜𝑜𝑑 𝐹𝑙𝑜𝑤
vasodilation in the setting of CO2
Results – Interpretation
Conclusions
1. Insufflation induced acid-base changes in the experimental model.
2. CEUS was able to identify changes that correlated to acid-base changes.
3. Observed changes in CEUS parameters seem to reflect vasodilatory response of the brain to hypercapnia.
4. CEUS is useful to evaluate fetal brain perfusion.
What now?
• Similar model was performed using premature sheep transferred to the The EXTra-uterine Environment for Neonatal Development (EXTEND) system
1. Partridge EA, Davey MG, Hornick MA, et al. Nat Commun. 2017;8:15112.