Magnetic Resonance Molecular Imaging And Spectroscopy Based On Nuclear Spin Singlet Order

Magnetic resonance spectroscopy(MRS)is a noninvasive technique for determining the concentrations and content of various metabolites in vivo.It can be used to continuously and dynamically investigate the signals of endogenous molecules related to energy and lesion metabolism in vivo,providing early diagnostic information on diseases.However,the magnetic resonance signals of endogenous molecules in routine ~1H MR spectra overlap significantly due to the diversity of endogenous molecules and the complexity of the environment.It is difficult for the routine ~1H MRS method to selectively probe the signals of endogenous molecules in vivo such as glutamate,glutamine,and glycine.This significantly limits the use of MRS in the study of metabolic and pathological molecular mechanisms.In this work,we proposed a Singlet-Filtered method based on Optimal Control pulses(SFOC)to selectively probe the signals of target molecules.This is accomplished by carefully manipulating and editing the multi-spin systems of the target molecules to prepare the spin singlet order.The method has been successfully applied in vivo to the selective detection of magnetic resonance signals from various endogenous molecules such as N-acetyl-aspartate,glutamate,glutamine,and lactate molecules,providing a direct experimental basis for accurately describing the relationship between metabolite molecular content and function.The main research contents of this paper are as follows:1.In Chapter 2,the singlet-filtered method based on optimal control pulse(SFOC)is proposed.The effectiveness of the SFOC method in preparing nuclear spin singlets in two-spin systems with different coupling types(two spin strong coupling,intermediate coupling,and weak coupling)and multi-spin systems was discussed,respectively.Taking the five-spin system of glutamate as an example,it has been theoretically and experimentally demonstrated that SFOC has much higher singlet-filtered efficiency in multi-spin systems than the pulse sequence in the literature,such as SLIC(Spin-Lock Induced Crossing)pulse sequence;The signals of various biochemical molecules(such as dopamine and taurine)were successfully distinguished in vitro using SFOC pulse sequence,providing an important theoretical and experimental basis for the detection of endogenous molecule signals in vivo.2.In Chapter 3,the SFOC-MRS pulse sequence,which is suitable for human MRI scanners,was developed by combining SFOC with routine MRS pulse.The characteristic signals of N-acetyl aspartate(NAA)were selectively probed in the brains of healthy subjects in vivo.The local p H were successfully determined by establishing a relationship between p H value and the characteristic signals.3.In Chapter 4,the SFOC method was further extended to selectively probe the signals of tumor metabolites(glutamate,glutamine,glycine,and lactate)in human brains in vivo.The SFOC-MRS pulse sequences for glutamate(Glu)and glutamine(Gln)were developed to separate the magnetic resonance signals of Glu and Gln,which are difficult to distinguish in the human brain’s routine ~1H MR spectra.The Glu/Gln magnetic resonance signals in the human brain in vivo were probed selectively by preparing the singlet order of the Glu/Gln five-spin system.By using the multi-spin manipulation method in SFOC to control the eight-spin system composed of glycine(Gly)and myo inositol(MI),the GFOC-MRS(Gly-Filtered sequence based on Optimal control pulse,GFOC)pulse sequence was developed to separate the signal of Gly at3.55 ppm(where MI and Gly signals usually overlap).The signals of Gly in healthy and tumor tissues of the human brain were successfully distinguished in vivo.The results show that the signal intensity of Gly in the tumor region was much higher than the intensity in the healthy region.Furthermore,the method of multi-spin system manipulation was applied to the selective detection of lactate(Lac).The LFOC-MRS(Lac-Filtered sequence based on Optimal Control)pulse sequence was developed to selectively probe the signals of Lac in the cerebrospinal fluid of healthy subjects in vivo.The experimental results show that LFOC-MRS sequence has higher sensitivity than the Point Resolved Spectra sequence(PRESS)method with long TE(Echo Echo).To investigate the relationship between the signal intensity and accumulation time of Lac,the LFOC-MRS pulse sequence was applied to human thigh muscle tissue.The findings revealed that anaerobic exercise was associated with Lac production,and Lac was still accumulated after exercise 30 minutes.4.In chapter 5,the singlet-filtered method was applied to several Nuclear Magnetic Resonance(NMR)Two Dimensional(2D)experiments and molecule magnetic resonance imaging.The molecularly targeted COSY and DOSY pulse sequences are developed by combining singlet-filtered method with routine 2D NMR pulses.The effectiveness and stability of these two methods were verified in in vitro samples.These methods are expected to probe COSY and DOSY signals of endogenous molecules in vivo.The molecularly targeted MRI/CSI(chemical shift imaging)pulse sequences were developed by combining the singlet-filtered method and two-dimensional MRI/CSI to image the target molecules.The effectiveness and stability of these techniques,which offer methodological support and an experimental framework for CSI and MRI of endogenous molecules in vivo,have been demonstrated in vitro.In conclusion,this work demonstrates that it is possible to selectively probe the signals of endogenous molecules in vivo using the singlet-filtered method based on optimal control pulse.The technique may provide the crucial biological information required for examining endogenous molecules,physiological processes,and disease-related metabolic pathways.