Title: "Modelling and modulating CSF-brain influx in pigs"
Summary:
My PhD project focused on developing an experimental and analysis protocol to study CSF flow and brain influx in pigs using in vivo SPECT imaging, through injection of the radiotracer Tc99m-DTPA into the cisterna magna. We also used ultrafast MR- encephalography (MREG) to measure brain pulsations and correlate them with brain influx obtained from SPECT. During scanning, pigs were monitored for arterial pressure, intracranial pressure, oxygen saturation, blood glucose, pCO2, respiration volume and frequency, and cortical activity via electroencephalography (EEG).
To apply kinetic modelling describing tracer movement in and out of the brain, we first identified brain and CSF compartments using non-negative matrix factorization. We then assessed the stability of a 1-tissue compartment model, finding stable influx parameters at 3h post-injection, with efflux beginning to appear at 4–5h and not reaching stability beyond 6h of scanning.
Using this framework, we compared the effects of different anesthetic regimens: propofol and ketamine plus dexmedetomidine (DEX) at two dose levels. Although low and high DEX produced similar total brain influx over 6h, their kinetic profiles diverged markedly: low DEX was associated with higher kinetic influx rates, whereas high DEX reduced influx kinetics but also decreased CSF flow, increasing tracer availability in the cranial space and ultimately sustaining comparable overall influx.
Finally, we applied kinetic modelling approximations to assess changes in brain influx under several physiological interventions: CO2 inhalation, intermittent apnea, and hypertonic and isotonic saline infusion. These interventions were subsequently reproduced in the MR environment to evaluate whether brain pulsations, as an indirect measure, correlate with brain influx measured directly by SPECT.
Principal supervisor during the PhD programme:
- Clinical Professor Gitte Moos Knudsen
- Neurobiology Research Unit, Rigshospitalet
Assessment Committee:- (Chairperson) Professor Birgitte Rahbek Kornum
Department of Neuroscience, University of Copenhagen, Denmark - Associate professor Tuomas O Lilius
Helsinki University, Finland - Associate professor Iben Lundgaard
Lund University, Sweden