Quatifications Of Chemical Exchange Saturation Transfer (CEST) MRI Based On Fitting Of Z-Spectral Line-Shape

Chemical exchange saturation transfer(CEST)is a novel MR technique that can detect certain compounds indirectly through water signal loss with high sensitivity.However,the change of water signal is not only caused by CEST,but also attributes to magnetization transfer contrast(MTC),direct water saturation(DS)and nuclear overhauser enhancement(NOE).Hence,precise quantification of CEST effect relies heavily on the removal of the contributions from superfluous sources.Typically,a spectral line of saturated water signal change,named Z-spectrum,generated by swapping a set of saturation pulse through certain frequency range,is employed as CEST spectral characteristics.CEST quantification through different extraction methods were discussed and studied based on Z-spectral line-shape.The main work is summarized as follows:1.Since Lorentzian Difference is unsuitable for larger B_1sat and tissues with high MT components,Voxel-wise Optimization of Pseudo Voigt Profile(VOPVP)is proposed to address these issues.VOPVP uses the Pseudo Voigt Profile,i.e.the weighted mixture of Gaussian and Lorentzian line-shape,as reference spectra,and then 5-pool Bloch-Mc Connell off-line simulation are utilized to calculate the coefficients of optimization compensation and save the results.The simulation illustrate that VOPVP is closer to the analytical solution which is taken as gold standard than LD,and the overestimation of CEST and NOE effect for LD fitting is greatly alleviated.In vivo experiments of mouse brain tumor further demonstrate that VOPVP method provided higher contrast SNR than LD method did at different B_1sat.Therefore,VOPVP is potential to be a robust and accurate quantization method based on Z-spectral Line-shape.2.Aiming at the issue of less significant CEST peak of amide proton caused by p H decrease in ischemic stroke,we present a quantization method which combines VOPVP and inverse Z-spectrum.This method takes the difference between the inverse of the experimental Z-spectrum and the inverse of the fitting Z-spectrum,replace the subtraction between fitting spectrum and experimental Z-spectra,to improve the signal contrast on the basis of project 1,MTR_Rex^{VOP VP}=1/Zexp-1/Z^VO_ref ^PVP.In simulation,two different exchange rates of amide protons(3.5 ppm)were used to mimic different p H in normal and lesion tissue.The results show that the proposed method detected larger difference between two types of tissue than MTR_asym and VOPVP method.According to the results of cerebral ischemia rat model,the proposed method was more sensitive than traditional methods for stroke detection.At various B_1satand time points,the proposed method provided higher contrast-to-noise raio in lesion region.3.To further improve the quantification of CEST signal,a quantitative analysis method combining 5-pool lorentzian fitting and inverse Z-spectrum is proposed.Specifically,5-pools lorentzian simulation(including water,amide(3.5 ppm),amine(2.2 ppm)and NOE(-3.5 ppm))of brain tissue parameters are first calculated offline and stored as initial value of Z-spectrum fitting.Then the difference between the inverse of Z-spectrum and the inverse of reference Z-spectrum is used as the CEST definite spectrum.The simulation results show that the new method detected larger difference than the saturation transfer difference and the 5-pool lorentzian fitting,and the line height and line width of different pools can be estimated.According to the results of cerebral ischemia rat model,the proposed method provided higher contrast-to-noise raio between ipsilateral striatum and contralateral under various acquisition conditions.In summary,this thesis proposed several CEST quantization methods based on Z-spectra line-shape fitting,which have been validated through simulation and animal experiments.These methods are robustness,accuracy and sensitivity,could have potential of being used in pre-clinical and clinical research.