Blood Oxygenation Level Dependent(BOLD) And Measurement Of Brain Temperature With Magnetic Resonance Spectroscopy For Ischemic Penumbra: Experimental Study

PartⅠ:The applications of BOLD in brain ischemic penumbra of monkey reversible MCAO modelObjective Cynomologous macaques were used to develop reversible middle cerebral artery occlusion(MCAO)model.To investigate the features and evolution of ischemic penumbra(IP)on blood oxygenation level dependent(BOLD)images and the effects of cerebral hemodynamic changes on BOLD.Methods Reversible MCAO model were developed in male cynomologous macaques(n=6)by using endovascular techniques.We used the following imaging protocols:CT perfusion,T2WI,DWI,PWI,as well as quantitative T2 map and T2^* map.Animals were scanned with CT and MRI between 1-1.5 hours after occlusion to 1h,3h,6h,12h,24h and 48h hours after reperfusion.Parameters included regional cerebral blood flow(rCBF),regional cerebral blood volume(rCBV),mean transit time(MTT),ADC,T2,T2^* and R2'.Quantitative T2 was linked to quantitative T2^* resulting in BOLD images(R2').The flow-compromised tissue was defined as the abonormal perfusion area on any PWI maps.According to the fate of the ischemic tissue,the flow-compromised tissue could be divided into three distinct areas:ischemic core,ischemic penumbra and regions of oligemia.Ischemic core:the region showed high signal intensity(SI)both on initial DWI and T2WI of hour 24 after reperfusion;ischemic penumbra:the region showed high SI on initial DWI and iso-SI on T2WI of hour 24 after reperfusion;the regions of oligemia:iso-SI both on initial DWI and T2WI of hours 24 after reperfusion.The effects of cerebral hemodynamic changes on BOLD were analyzed using multiple linear regression. Immediately after killing animals,the brains were removed and sliced fresh into axial 5-mm-thick axial slabs and stained with 2,3,5-triphenyltetrazolium chloride(TTC).Results(1)Reversible MCAO model were demonstrated successful in four cynomologous macaques.T2WI derived lesion volumes in hour 24 after reperfusion were similar to those of infarct measured on TTC.However,T2WI derived lesion volumes were smaller than the volumes of high SI on initial DWI about 28%.(2)The absolute perfusion values derived from CTP and PWI demonstrated definitely different.The discrimination disappeared when the relative ratios were considered. (3)During the MCAO,the SI of ischemic core,ischemic penumbra and regions of oligemia on R2' were different significantly.Strongest negative BOLD appeared within the regions of oligemia,then in ischemic penumbra.No remarkably negative BOLD could be detected within the regions of ischemic core.(4)Afer reperfusion, ischemic penumbra and regions of oligemia on R2' showed different time course.The bold effct changed dramatically from slight negative bold to positive in the region of ischemic core.The negative bold persisted during the reperfusion in the areas of ischemic penumbra and oligemia,and demonstrated a tendency stronger over time.(5)rCBF and MTT showed negative and positive influence on the SI on R2' respectively.Conculsion(1)During the MCAO,negative BOLD can be used to distinguish the ischemic core from ischemic penumbra and regions of oligemia,and to assess viability of brain tissue.(2)Afer reperfusion,the persistent negative bold sugest the tissue being salvaged while loss of negative blod or positive bold appeared imply tissue being dead.(3)rCBF and MTT are both important factors on BOLD effect.PartⅡ:Measurement of Brain Temperature with Magnetic Resonance Spectroscopy in brain ischemic penumbra of monkey reversible MCAO modelObjective To establish the modified equation between brain temperature and chemical shift of NAA.To investigate the features and evolution of ischemic penumbra(IP)in brain temperature measured with magnetic resonance spectroscopy and the influence on brain temperature from cerebral hemodynamic changes.Methods To develope the MRI-compatible thermostatic control system,and assess the precision and stability of the sytem.To establish the modified brain temperature and NAA form through vitro experiment.To measure the brain temperature in flow-compromised tissue in monkey transient MCAO model and normal temperature in the controls.The effects of cerebral hemodynamic changes on brain temperature were analyzed using multiple linear regression.Results(1)The MRI-compatible thermostatic control system showed high performance in precision and stability.The chemical shift of NAA therefore appeared to vary with temperature,and a modified version of Eq.was given by:T=37+100(CSN_NAA-2.039).(2)The normal brain temperature of monkeys was 37.16℃with no different between bilateral hemispheres.(3)After MCAO, temperature in the flow compromised tissue showed higher than those in contralateral hemisphere and normal monkeys.Temperature gradients could be found within the flow compromised region.Highest brain temperature appeared in ischemic penumbra,then the ischemic core and region of oligemia.(4)In the early stage after reperfusion,temperature in the flow compromised tissue decreased in different levels,most significant decrease in ischemic core.In the late stage,after reperfusion,the temperature within region of ischemic penumbra and oligemia recovered to normal while temperature within the ischemic core elevated again.(5) rCBF showed negative influence on brain temperature.Conculsion(1)^H MRS can be used to measure brain temperature noninvasively and to disclose the the temperature gradient within flow compromised areas.(2) rCBF and MTT are both important factors on brain temperature in monkey reversible MCAO model.Bold is helpful for understanding the changes of brain temperature.