Research On Temperature Measurement Approach And Key Technology Of Magnetic Nanoparticles Based On Multi-Physical Channels

Temperature is an important characterization of life activities.Accurate measurement of temperature changes caused by physiological and pathological activities of life is crucial for life science research.The remarkable and efficient temperature-to-magnetization transition characteristic of magnetic nanoparticles(MNPs)demonstrates its potential as temperature probes in vivo.However,the existing magnetic temperature measurement has problems of low signal-to-noise ratio(SNR),low temperature sensitivity,high-frequency relaxation,MNPs’ concentration coupling,and how to achieve long-distance and high-SNR signal transmission.To solve these problems and expand the needs of real-time temperature imaging in the future,this thesis proposes and systematically studies the corresponding KHz,MHz and GHz physical channels based on the magnetic physics theories such as magnetic particle spectrum(MPS),magnetic resonance imaging(MRI)and electron paramagnetic resonance(EPR),so as to explore the mechanism and approach of transmitting MNPs’ temperature information with high SNR.These approaches provide theoretical support and technical reserve for temperature imaging in the field of life medicine such as cell thermometry and tumor hyperthermia in the future.Aiming at the problem of low SNR of high-order harmonics in MPS under KHz-AC excitation,a temperature measurement approach excited by dual-frequency AC magnetic field is proposed,which efficiently improves the temperature measurement accuracy when the system power is limited.By analyzing the magnetization response of MNPs under dualfrequency excitation,the dual-harmonic model and multi-harmonic model are constructed,respectively.The influence of the amplitude and frequency of the excitation magnetic field and the magnetic detection sensor on the temperature measurement is analyzed,and the optimized system parameters are then obtained.A dual-frequency excitation temperature measurement system is built accordingly.In order to avoid the influence of the frequency dependence of the induction coil,the tunnel magnetoresistive sensor is used as the detection element.The experimental results show that the temperature accuracy of the dual-harmonic model reaches 0.02 K,and the multi-harmonic model reaches 0.015 K.To solve the problem that the information transmission process of harmonic amplitude is susceptible to noise interference,this thesis combines the MNPs with MRI technology and proposes a visual high-precision temperature measurement in MHz channel.By studying the magnetization behavior of the MNPs-water solution in MRI,a temperature measurement model based on the paramagnetic phase of MNPs is established.Various factors affecting the phase are analyzed in detail,and the MNPs with the highest temperature sensitivity are selected for experiments.The flip-angle and echo time are optimized to improve the SNR.The reference water-model and the field spatial distribution fitting algorithm are used to reduce the influence of the field drift.The results show that the 3 TMRI can recognize the change of concentration,and the temperature accuracy is better than0.1 K.This approach successfully modulates the static magnetization signal of MNPs to the high-frequency channel of proton resonance,which improves the sensitivity of the magnetic detection signal and avoids the influence of high-frequency relaxation of MNPs.To eliminate the interference of the concentration coupling of temperature-sensitive parameters,a high-precision temperature measurement approach in GHz-channel is proposed based on EPR.By studying the effect of temperature on the magnetic anisotropy field of MNPs,the temperature measurement models based on g-value and FWHM(full width at half maximum)are established,respectively.Concentration experiments show that the g-value is independent of MNPs’ concentration,but the FWHM and SNR are greatly affected by it.The effects of concentration and size of MNP on temperature sensitivity of gvalue and FWHM are further analyzed.Different data analysis algorithms are used to estimate temperature.The results show that the temperature sensitivity of 15-nm MNPs is the best.When the Fe concentration is 5 mg/ml,the optimal accuracy of the g-value model reaches 0.07 K and the FWHM model is 0.04 K.Finally,a cell experiment is designed and the cell temperature rise of 1 K stimulated by noradrenaline is preliminary measured.In conclusion,this work deeply studies the mechanism and methods of temperature measurement based on MNPs under multi-physical channels,solves several key problems of current measurement technology,and provides theoretical and technical support for further in vivo temperature measurement and even imaging.