Cerebral Monitoring after Asphyxia:Tissue Oxygenation and Cerebral

Blood Flow

Mioara D. Manole

University of PittsburghSafar Center for Resuscitation Research

Carnegie Mellon University, NMR Center for Biomedical Research

Aims for MNTP course

• To learn a variety of new methods for cerebral monitoring

– Cerebral oxygenation (Tissue sensors)– White matter tracts post injury (DTI)– Water content of the brain (DWI)– Cerebral microvasculature (two photon

microscopy)

Cerebral blood flow after pediatric asphyxial CA

ASL-MRI

STUDY GROUPS

CA

Sham

PREPARATION

Intubation

Catheters

BASELINE

CBF

ASL-MRI

9 MIN ASPHYXIA

RESUSCITATION

Chest compressions

Epinephrine

Sodium bicarbonate

Normal Saline

POST RESUSCITATION

Serial CBF

5, 10, 15, 30 min

1, 1.5, 2, 2.5 h

Regional CBF After Asphyxial CA in Immature 17 Day Old Rats*

SHAM CA

Baseline

5 min

15 min

30 min

10 min

1h

1.5 h

2 h

2.5 h*Manole et al, JCBFM 2009

Early hyperemia

(subcortical)

Hypoperfusion

(cortex)

Aim 1Assess brain tissue oxygenation in

cortex and thalamus

• Polarographic oxygen sensor• Assess the sampling volume of the oxygen

sensor• Measure brain tissue oxygen tension in cortex

and thalamus in our model of cardiac arrest

Oxygen sensor

• 10-50 μm tip

• can sample at cellular or vascular level

Air

Nitrogen in water

• 30 μm increments

• record pO2

Sampling volume for oxygen sensor

-Time constant

-Sampling volume

-Time constant 0.23 s

-Sampling volume 124 μm

PbO2 during Cardiac Arrest

0

10

20

30

40

50

60

70

80

Time (min)

Pb

O2

(mm

Hg

)

0.210.5 Asphyxia

-110

-90

-70

-50

-30

-10

10

30

CO

% C

HA

NG

E

0 100 200 300 400 500 600

Time (s)

PND 17

gasping

PbO2 after ROSC: Cortex

Time (min)

Baseline 0 5 10 15 30 60 120 150 180

Cor

tical

PbO

2 (

mm

Hg)

0

50

100

150

200

250

300

350

No anestesiaFentanyl

Twofold increase in PbO2 in the cortex

Decrease to values of 20 mm Hg after 30 min

Time (min)

Baseline 0 5 10 15 30 60 120 150 180

Tha

lam

ic P

bO2 (

mm

Hg)

0

50

100

150

200

250

300

350No anesthesiaFentanyl

PbO2 after ROSCThalamus

Fivefold increase in PbO2 in the thalamus

• DTI

• Two photon microscopy

Aim 2Explore other imaging modalities

DTI• DTI studio

• Explore DTI

Two photon microscopy

• Cortical vascular system

• Fluorescein Dextran injection

• Excitation 860 nm/ emission 500-500 nmprojections over the first 100um 300um

Carnegie Mellon University Pittsburgh NMR Center

Lesley Foley

Kevin Hitchens

Chien Ho

Safar Center for Resuscitation Research

Robert Clark

Patrick Kochanek

Hülya Bayır

Keri Feldman

Robert Hickey

Support: NIH K08HD058798 (MM), T32NS07485-02 (PMK), HD045968 (RSBC), P41EB-001977 (CH), Laerdal Foundation (MM)

Pittsburgh Center for Free Radical and Antioxidant Health

Valerian Kagan

Hülya Bayır University of Pennsylvania

William Armstead

Synzyme Technologies

Li Ma

Carleton Hsia

MNTP programSeong Gi Kim

Alberto Vasquez

Hiro Fukuta

Justin Crawley

Kwan-Jin Jung

Oxygen sensor– diffusion of oxygen through a

silicone membrane – oxygen reducing cathode

which is polarized against an internal Ag/AgCl anode

Ag + Cl- = AgCl + e- (anode)

O2 + 2H2O +4e- = 4 OH- (cathode)

Oxygen sensor

– The flow of electrons from the anode to the oxygen reducing cathode reflects linearly the oxygen partial pressure around the sensor tip

– The current is measured by a high quality picoammeter.

Oxygen sensor:response time and sampling

• Response time is influenced by:– Electrode diameter– Membrane thickness– Membrane diffusion coefficient

• Sampling distance 2-4 times tip diameter

Sampling from Cortex and Thalamus

– Cortex coordinates• 2 mm lateral • 1.5 mm deep • 3.14 mm posterior

– Thalamus coordinates• 2.5 mm lateral• 6 mm deep• 3.14 mm posterior

*

*

RA 50% Oxygen 100% Oxygen

Tha

lam

ic b

rain

tiss

ue P

bO2

(mm

Hg)

0

50

100

150

200

250

IsofluraneFentanyl

*

*

*

RA 50% Oxygen 100% Oxygen

Cor

tical

Bra

in T

issu

e O

2 (m

m H

g)

0

50

100

150

200

250IsofluraneFentanyl

PbO2 during resuscitation

-150

-100

-50

0

50

100

150

200

Pb

O2

(mm

Hg

)

CPR ROSC

22 s

PbO2 after ROSC: Cortex

Time (min)

Baseline 0 5 10 15 30 60 120 150 180

Cor

tical

PbO

2 (

mm

Hg)

0

50

100

150

200

250

300

350

No anestesiaFentanyl

Twofold increase in PbO2 in the cortex

Decrease to values of 20 mm Hg after 30 min

Time (min)

Baseline 0 5 10 15 30 60 120 150 180

Tha

lam

ic P

bO2 (

mm

Hg)

0

50

100

150

200

250

300

350No anesthesiaFentanyl

PbO2 after ROSCThalamus

Fivefold increase in PbO2 in the thalamus

Oxygen Titration in the Post Cardiac Arrest Period

Thalamic PbO2

Oxygen concentration (%)

50% 100% 21%

Tha

lam

ic P

bO2

(mm

Hg)

0

20

40

60

80

*

O2 sat 80%

Hb saturation- Rate limiting factor for

oxygen delivery?

Oxygen Titration in the Post Cardiac Arrest Period

Cortical PbO2

Oxygen concentration (%)

50% 100% 21%

Cor

tical

PbO

2 (m

m H

g)

0

20

40

60

80

*