List of issues in brain tumour CEST.

1. Glucose concentration.
   
• What are the values we should expect in the brain, and what is the minimum we can detect?
• Is 2dg going to help? What's is the concentration in this case? (dynamics of 2dg)
• What's the uptake rate difference between tumours and healthy tissue? Is this difference within the range we can detect? (pet 18f-fdg dynamics would help).
• Glucose delivery. Do we really know if IP injections work? Blood tests.
  
  
2. Anaesthetics.
• What is the best drug to use in relation to the glucose and pH (lactate?) and other metabolic reactions? 
• "Lactate levels in the brain are elevated upon exposure to volatile anesthetics: A microdialysis study." HornT, Klein J.
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• Is the lactate affecting our CEST measurements by reducing the pH? How much does the pH change? Enough to alter the transfer rate?
• Considerations of threshold values. "Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 fimoUg; below 17 fimollg, intracellular pH remained stable at 6.8-6.9, whereas above 22 /imol/g, intracellular pH decreased maximally to about 62. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 /unol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage. (Stroke 1990^21:936-942)"  

  Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils. Combs DJ, Dempsey RJ, Maley M, Donaldson D, Smith C.

  
  
3. Tumour cell type.
• Even if all above works out favourably, having a spread type tumour invalidates the CEST MRI method as a detection tool due to the lack of contrast. 
• Is it worth following this technique if solid type tumours are of low clinical interest?