Cerebral Monitoring after Asphyxia: Tissue Oxygenation and Cerebral Blood Flow

1. Cerebral Monitoring after Asphyxia:Tissue Oxygenation and Cerebral Blood Flow Mioara D. Manole University of Pittsburgh Safar Center for Resuscitation Research Carnegie Mellon University, NMR Center for Biomedical Research

2. 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)

3. Cerebral blood flow after pediatric asphyxial CAASL-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

4. Baseline SHAM CA 5 min 10 min Early hyperemia (subcortical) 15 min 30 min 1h Hypoperfusion (cortex) 1.5 h 2 h 2.5 h Regional CBF After Asphyxial CA in Immature 17 Day Old Rats* *Manole et al, JCBFM 2009

5. 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

6. Oxygen sensor • 10-50 μm tip • can sample at cellular or vascular level

7. 30 μm increments • record pO2 Air Nitrogen in water

8. Sampling volume for oxygen sensor • Time constant • Sampling volume • Time constant 0.23 s • Sampling volume 124 μm

9. 30 10 -10 -30 CO % CHANGE -50 -70 -90 -110 0 100 200 300 400 500 600 Time (s) gasping PND 17 PbO2 during Cardiac Arrest 0.5 0.21 Asphyxia

10. PbO2 after ROSC: Cortex Twofold increase in PbO2 in the cortex Decrease to values of 20 mm Hg after 30 min

11. PbO2 after ROSCThalamus Fivefold increase in PbO2 in the thalamus

12. Aim 2Explore other imaging modalities • DTI • Two photon microscopy

13. DTI • DTI studio • Explore DTI

14. projections over the first 100um 300um Two photon microscopy • Cortical vascular system • Fluorescein Dextran injection • Excitation 860 nm/ emission 500-500 nm

15. 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 • Pittsburgh Center for Free Radical and Antioxidant Health • Valerian Kagan • Hülya Bayır • MNTP program • Seong Gi Kim • Alberto Vasquez • Hiro Fukuta • Justin Crawley • Kwan-Jin Jung • University of Pennsylvania • William Armstead • Synzyme Technologies • Li Ma • Carleton Hsia Support: NIH K08HD058798 (MM), T32NS07485-02 (PMK), HD045968 (RSBC), P41EB-001977 (CH), Laerdal Foundation (MM)

16. 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)

17. 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.

18. 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

19. 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 * *

21. * * *

22. PbO2 during resuscitation CPR ROSC 22 s

23. PbO2 after ROSC: Cortex Twofold increase in PbO2 in the cortex Decrease to values of 20 mm Hg after 30 min

24. PbO2 after ROSCThalamus Fivefold increase in PbO2 in the thalamus

25. Oxygen Titration in the Post Cardiac Arrest PeriodThalamic PbO2 O2 sat 80% Hb saturation- Rate limiting factor for oxygen delivery? *

26. Oxygen Titration in the Post Cardiac Arrest PeriodCortical PbO2 *