Using MRI Compatible Oxy Lite TM Fiber-optic Microprobes To Verify The Reliability Of Detecting The Oxygenation Changes In Rats C6 Glioma By Steady-state Free Precession FMRI

Objective: Tumor hypoxia is one of the key factors that affect the efficacy of radiotherapy.Thus,the ability to detect dynamic changes in oxygen saturation level within tumor is of great importance.Steady-state free precession(SSFP)sequence has recently been employed for functional MRI(fMRI).In our study,we aim to verify the reliability of SSFP fMRI for detecting oxygen saturation level changes.To achieve this,we compare image signal variations with direct measurements obtained from rat C6 glioma using MRI compatible fiber-optic microprobes.Materials and Methods: A total of 30 male Sprague-Dawley rats were used to establish the subcutaneous C6 glioma model.MRI compatible OxyLiteTM fiber-optic microprobes were embedded in the tumor after anesthesia.The rats were then examined in the prone position using a clinical 3.0 T whole-body MRI system(Ingenia,Philips Healthcare,the Netherlands).A dStream small extremity 8-channel coil was used for signal reception.Acquisition parameters were as follows: TR/TE=6.9ms/3.4ms;flip angle=70°;FOV=80mm×80mm;acquisition matrix=136×134;slice thickness=2mm(four slices);number of dynamic scans=100.SSFP fMRI scans were performed with Carbogen inhalation while a series of tissue pO2 values were recorded simultaneously in real time using the fiber-optic microprobes.Image data was processed using non-hemodynamic response function(non-HRF)analysis provided by AFNI software.A spherical region of interest(ROI)with a 2mm diameter was placed at the tip of the fiber-optic microprobe to determine the T value and percentage signal change(PSC).The mean difference of pO2(ΔpO2)before(pO2-air)and after(pO2-car)Carbogen inhalation in the ROI was calculated.The difference between pO2-air and pO2-car was tested by Wilcoxon matched-pair signed rank test.Lastly,we investigated the correlation between ΔpO2 and T value,as well as between ΔpO2 and PSC.Results: We obtained p O2 values before and after Carbogen inhalation at 24 different locations in the tumor region during SSFP fMRI scan.The experimental results,shown in the format of [median(interquartile range)],were as follows: pO2-air= 0.495(5.350)mmHg,pO2-car=0.490(14.898)mmHg,Δp O2=0.550(5.130)mmHg,T value=2.326(6.735),PSC value=0.857(3.269)%.The mean value of p O2 significantly increased after Carbogen inhalation(z=3.329,p=0.001).The mean value of ΔpO2 measured at all of the 24 tumor locations correlated positively both to T value(Spearman’ r=0.474,p=0.019)and PSC value(Spearman’ r=0.463,p=0.023).Conclusions:To conclude,fMRI using steady-state free precession(SSFP)is able to track changes in oxygen saturation level in rat glioma,and hence has the potential to detect tumor hypoxia.