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Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier 1,2 , Anush Sridharan 1 , Kendall Lawrence 1 , Juan S. Martin-Saavedra 1 , Marcus G. Davey 1,2 , Beverly G. Coleman 1,2 , and Alan W. Flake 1,2 1 The Children’s Hospital of Philadelphia 2 Perelman School of Medicine, University of Pennsylvania

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Page 1: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 2: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

Disclosures

• No financial disclosures

Page 3: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 4: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 5: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

Materials & Methods - Surgery

POD 2-3Experimental surgery,

continuous monitoring

GA 101-106Fetal carotid artery catheter

Study period

Page 6: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 7: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

Materials & Methods- CEUS

GE Loqiq E9

GE C2-9

transducer

0.1-0.3mLContrastinjection

Page 8: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall
Page 9: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall
Page 10: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

Materials & Methods – CEUS Variables

Time (s)

Ech

o-P

ow

er (

a.u

.)

Transit Time

Rise Time

Time to Peak

Fall Time

Page 11: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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)

Page 12: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 13: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 14: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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

Page 15: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

𝑇𝑟𝑎𝑛𝑠𝑖𝑡 𝑇𝑖𝑚𝑒 =𝐶𝑒𝑟𝑒𝑏𝑟𝑎𝑙 𝐵𝑙𝑜𝑜𝑑 𝑉𝑜𝑙𝑢𝑚𝑒

𝐶𝑒𝑟𝑒𝑏𝑟𝑎𝑙 𝐵𝑙𝑜𝑜𝑑 𝐹𝑙𝑜𝑤

vasodilation in the setting of CO2

Results – Interpretation

Page 16: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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.

Page 17: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

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.

Page 18: Contrast-Enhanced Ultrasound Evaluation of Fetal Brain ... · Contrast-Enhanced Ultrasound Evaluation of Fetal Brain Perfusion Parameters Ryne A. Didier1,2, Anush Sridharan1, Kendall

Thanks

Email: [email protected] S. Martin-Saavedra

The Children’s Hospital of Philadelphia, USA