MODELING OF TEMPERATURE WITHIN THE NEONATAL HEAD SUBJECTED TO TRANSCRANIAL CONDUCTIVE COOLING

1. MODELING OF TEMPERATURE WITHIN THE NEONATAL HEAD SUBJECTED TO TRANSCRANIAL CONDUCTIVE COOLING G Van Leeuwen1, J Hand1 D Edwards2 and D Azzopardi2 1 Radiological Sciences Unit, Dept of Imaging,& 2 Department of Paediatrics & Neonatal Medicine Imperial College School of Medicine Hammersmith Hospital, London

2. Hypothermal neural rescue therapy • studies of cerebral injury have shown that promoting moderate brain cooling may reduce damage and improve functional outcome • preliminary clinical trials of hypothermic neural protection in newborn infants suffering perinatal asphyxia are underway

3. Hypothermal neural rescue therapy • injury to deep brain structures predicts severe neurological impairment • cortical injury is relatively benign • MR studies have shown basal ganglia are significantly warmer than superficial cerebral tissues • few data available regarding • temperature distribution within the newborn brain • effect of local or systemic cooling • such data are difficult to acquire • measurements by MR or MW radiometry?

4. Hypothermal neural rescue therapy • how to cool? • localised head cooling? • whole body cooling? • In this work we have • used a thermal model to predict 3D temperature distributions in an anatomically realistic model • tested sensitivity of results to • geometry and description of heat transfer • brain perfusion • thermal conductivity

5. Baby head model Orthogonal cross-sections within the 3 dimensional MR data set on which the temperature distributions are contoured

6. Assumptions made in the model water cap temperature Twater = 10 oC (isothermal boundary) air temperature Tair = 32 oC infant’s core temperature Tcore = 37/34 oC

7. dT dt (k T) + B + M   r c = Bioheat transfer equation (Pennes, 1948) rate of increase in energy per unit volume due to metabolism rate of loss of energy per unit volume due to perfusion: “heat sink” : B = - w cblood (T -Tcore) rate of change of energy per unit volume due to thermal conduction

8. Tissue properties

9. Head cooling only 37 oC 37 oC 27 oC Twater_cap = 10 oC Tcore = 37 oC contours at 2 oC intervals 37 oC

10. Head + ‘whole body’ cooling 34 oC 34 oC 24 oC Twater_cap = 10 oC Tcore = 34 oC contours at 2 oC intervals 34 oC

11. Reduced adult head models • 11/15 scale model from T1 weighted MRI adult head data set • heat sink • discrete vessels • additional data regarding cerebral vasculature from MR angiography • visible vessels traced and small vessels added using a vessel generation • algorithm (vessels down to 0.2 mm diameter included)

12. Discrete arterial and venous vessel determined by MRA

13. Discrete arterial and venous vessel networks

14. Reduced adult head - heatsink model 37 oC 37 oC Twater_cap = 10 oC Tcore = 37 oC contours at 2 oC intervals 27 oC 37 oC

15. Reduced adult head - heatsink model 34 oC 34 oC Twater_cap = 10 oC Tcore = 34 oC contours at 2 oC intervals 24 oC 34 oC

16. Reduced adult head - discrete vessels 37 oC 37 oC Twater_cap = 10 oC Tcore = 37 oC contours at 2 oC intervals 27 oC 37 oC

17. Reduced adult head - discrete vessels 34 oC 34 oC Twater_cap = 10 oC Tcore = 34 oC contours at 2 oC intervals 24 oC 34 oC

18. Baby head Reduced adult head discrete vessels heatsink heatsink Tcore = 34 oC Tcore = 37 oC

19. Temperature profiles

20. Temperature profiles - perfusion and conductivity changes ‘low’ w = 0.75 x ‘normal’ w for brain ‘high’ k = 3 x ‘normal’ k for skin/skull

21. Summary (1) • the general predictions of the thermal modelling are robust • transcranial conductive cooling is effective in lowering the temperature significantly only in tissues up to approximately 20 mm deep • cooling of superficial brain tissues • minimal effect in diencephalon • must be combined with whole body cooling to reduce temperature in diencephalon • Reiterate key goals • Thanks

22. A 2nd application of the thermal model • in the development of multi-frequency microwave radiometry to monitor deep brain temperature during mild hypothermal neural rescue therapy • Reiterate key goals • Thanks

23. Microwave radiometry Radiometer 1GHz < fi (i= 1, 5) < 4GHz Dfi = 0.4MHz between 1 and 4 GHz Antenna Pant,i kDfi TB,i= i = 1,···,5 TB,iare known asbrightness temperatures

24. TB,i = antenna view fieldWi (r)T(r)dv 1 GHz 2 GHz Weighting functions Wi (r) 3 GHz 4 GHz

25. Temp. T(z) Tpeak T0 Tw 0 zpeak Depth z Bolus Brain TB,i = antenna view fieldWi (r)T(r)dv Equi-temperature shell model T(z) = T0 + dT [exp(-z/a) – exp(-z/b)]

26. Temperature profile retrieval assume initial temperature profile (a, b, dT) random fluctuations measure set of brightness temperatures calculate corresponding brightness temperatures compare predicted and measured brightness temperatures adjust parameters a ,b, dT for best fit temperature profile predicted temperature profile and 2 s estimate of precision

27. Summary (2) • thermal model suggests equi-temperature shell model is a good approximation to T(z) within the baby head • a good approximation of the predicted temperature profile can be obtained using 3 parameters • T(z) = T0 + dT [exp(-z/a) – exp(-z/b)] • used in iterative solution to inverse problem to retrieve the temperature profile beneath the radiometer antenna • Reiterate key goals • Thanks