| Real time and in situ acquisition of multi angle information such as living tissue structure,molecular metabolism and microenvironment(such as temperature,pH,electrolyte level,etc.)related to biological diseases is the basis of accurate diagnosis and treatment.At present,conventional MRI uses high-sensitivity water proton(1H)spin signal to provide the structural image of living tissue.Heteronuclear(13C,31P,23Na,etc.)probe molecular MRI is an important means to obtain the metabolism and microenvironment properties of living tissues.For example,13C MRI can quantitatively characterize the metabolism of biological or drug small molecules.However,restricted by the sensitivity bottleneck,the above heteronuclear imaging is very difficult.As a particularly important method in the field of NMR,DNP technology has become a hot research direction in this field because it can improve the sensitivity of NMR by several orders of magnitude.DNP technology is a double resonance technology based on electron-nuclear spin.It is a method to realize electron nuclear spin polarization transfer and nuclear polarization enhancement through the joint manipulation of microwave and RF fields.In principle,the signal intensity can be improved by 2～3 orders of magnitude by using this method.Combined with low-temperature electron polarization enhancement means,the magnetic resonance signal of heteronuclear(15N,13C,etc.)can be increased to 3～4 orders of magnitude,so as to make heteronuclear MRS/MRI possible.According to the application requirements of heteronuclear magnetic resonance spectroscopy/imaging,key core components including DNP probe,low losstransmission gradient waveguide,sapphire waveguide box window and so on are developed.A high field DNP device is integrated,which has the detection function of heteronuclear trace liquid molecules,realizes the NMR signal enhancement of in-situ heteronuclear liquid molecules,and verifies the feasibility of DNP technology in high field.The device can also realize low-temperature hyperpolarization and can be used for biomolecular metabolic imaging.Using DNP technology and low temperature technology,the maximum signal enhancement of 13C heteronuclear molecule can be obtained by 4 orders of magnitude.Comparing the difference of MRI imaging quality between hyperpolarization and thermal equilibrium,it is verified that this method has great potential in the field of heteronuclear molecular imaging technology.Specifically,the research work and innovations of this paper are as follows:1)According to the requirements of high field DNP device,a general console system of high field DNP is developed by using distributed parallel control architecture.Using the scheme of DDS and PLL,a 20～600 MHz RF signal source is developed,which meets the requirements of broadband,fast switching and high-resolution signal source.Key components such as preamplifier are designed to ensure the reliability of RF signal transmission and meet the basic functional requirements of weak signal amplification and transceiver switching received in high field DNP experiment.2)For the low loss transmission of high-frequency microwave,the over-mode transmission scheme is adopted,and the WR6-WR28 graded waveguide is designed.Under the microwave frequency of 140 GHz,the total length of the transmission line is more than 2.4 m and less than 7 dB.Aiming at the problem of vacuum sealing,a sapphire waveguide box window is designed to meet the broadband transmission at 140± 10 GHz,achieve good sealing,have good structural stability,and meet the special requirements of low-temperature DNP system.3)The developed high field DNP device has the functions of in-situ room temperature liquid DNP spectrometer and low temperature D-DNP polarization.According to the functional requirements of in-situ liquid DNP for simultaneous and efficient excitation of nuclear magnetic resonance and electron paramagnetic resonance,a 140 GHz/53.47 MHz double resonance cavity with high Q value is developed by using the design scheme of single coil double resonance,which has high conversion efficiency of microwave field and RF field,uniform magnetic field distribution in the sample area and weak electric field.It has low heating effect and good RF characteristics,which meets the power requirements of room temperature liquid experiment.According to the probe design requirements of low-temperature D-DNP polarization for large sample quantity,the technical means of over-mode microwave transmission and mirror radiation samples are adopted to meet the excitation of electronic transition at low temperature and have a large sample quantity at the same time.The RF network scheme with near tuning and matching and far end further optimized is adopted to meet the acquisition function of NMR signal at low temperature and long distance.In addition,the low-temperature probe also has good sealing,low heat load characteristics and expandable functions.4)For the function of in-situ room temperature liquid DNP spectrometer,the traveling wave tube amplifier is used as the microwave output scheme to realize the high-power microwave output with the output greater than 3 W in the bandwidth range of 140±1 GHz.The adjustable attenuator and field scanning module are integrated to meet the research needs of variable power,field scanning and other special DNP-NMR applications of high field in-situ liquid DNP system.Aiming at the polarization function of low-temperature D-DNP,a low-temperature cooling system is designed to realize that the minimum temperature of the system is less than 1.8 K.Further,the rapid dissolution device is used to realize the rapid dissolution and transfer about 7 seconds after low-temperature polarization for subsequent MRI/MRS application research,which can retain the high polarity of the target heteronucleus to the greatest extent.5)Based on high field DNP device,relevant application research is carried out.Aiming at the function of in-situ room temperature liquid DNP,the paramagnetic characteristics of unpaired electrons in solution are studied by using the field scanning function of the device and DNP enhancement technology.The relationship between DNP enhancement and magnetic field,polarization time and microwave power is optimized,and the maximum DNP enhancement multiple of about 150 times is obtained.For the function of low-temperature hyperpolarization,relevant studies were carried out at low temperature,and the DNP enhancement characteristics of TEMPOL and trityl radicals at low temperature were studied.By optimizing the microwave frequency and polarization time,a high degree of polarization of more than 30%is obtained.Relevant MRI/MRS studies were carried out using dissolved hyperpolarized liquid samples.The signal enhancement of more than 29000(4 orders of magnitude)was obtained by comparing the dissolved hyperpolarized liquid sample with the sample signal in thermal equilibrium;Through MRI experiments,huge differences in image quality are obtained,which verifies the feasibility of this method in heteronuclear metabolic imaging. |
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