本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振...本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振成像(Magnetic Resonance Imaging,MRI)扫描仪,对经 1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)急性造模前及造模后第3、10天的小鼠黑质、皮层及海马进行扫描,计算弛豫时间 T1、T2、MTRasym(magnetization transfer ratio based on asymmetry analysis)、MTRrex(magnetization transfer ratio yielding Rex)、AREX(apparent exchange-dependent relaxation)及5池拟合后的胺峰面积 Areaamine、酰胺峰面积 Areaamide.结果显示仅黑质中融合了倒Z谱分析和5池洛仑兹拟合所得的量化指标 MTRrex、AREX及Areaamine在造模后显著减小,与黑质免疫组化结果一致,而 T1、T2以及基于Z谱非对称性分析的 MTRasym未见统计学差异,这表明此量化方式消除了直接饱和效应及磁化转移效应的影响,准确性上要优于Z谱非对称分析法,更能正确地提示帕金森氏病黑质的变化.展开更多
Nuclear magnetic resonance(NMR)spectroscopy has provided many powerful tools for the study of dynamic processes.Among the reported methods,chemical exchange saturation transfer(CEST)is more suitable for systems with s...Nuclear magnetic resonance(NMR)spectroscopy has provided many powerful tools for the study of dynamic processes.Among the reported methods,chemical exchange saturation transfer(CEST)is more suitable for systems with slow exchange rates,and there will be promising in the detection and dynamic mechanism of metastable substances.It has been widely used in magnetic resonance imaging(MRI),however whether it is applicable in the field of chemical kinetics needs more examples.Here we studied,as a proof of concept,the kinetics of the slow chemical exchange between the two N-methyl protons of N,N-dimethylacetylamide(DMA),exploiting QUantifying Exchange using Z-spectrum(QUEZS)and QUantifying Exchange using Saturation Time(QUEST)methods.It turned out that both of QUEZS and QUEST could give the corresponding exchange rates,showcasing the capability of this method to provide accurate kinetic data under a range of temperatures.Our results clearly demonstrated the reliability of CEST-based techniques as a tool for dynamic kinetics by NMR.展开更多
Diamagnetic CEST(diaCEST)MRI contrast agents(CAs)have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters,even after the ag...Diamagnetic CEST(diaCEST)MRI contrast agents(CAs)have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters,even after the agent is administered.However,the low efficiency and small solute−solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications.Low efficiency demands high dosage,while small offset invites unwanted interference from the endogenous metabolites present in the human body.So far,the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate.Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA.It was recently shown that hydrothermally synthesized carbon nanodots(CDs)have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs.Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute−solvent offset and contrast efficiency.In particular,we demonstrate 300%enhancement in offset and 100%enhancement in efficiency following the formation of carbon-dots from a urea−citric acid mixture.展开更多
The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particula...The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particularly significant,offering detailed insights into the kinetic,thermodynamic,and structural aspects of biological function.Many critical biological processes,including enzyme catalysis,protein folding,ligand binding,and allosteric regulation,operate within this timescale.Nuclear magnetic resonance(NMR)spectroscopy is a powerful technique for probing molecular dynamics in this time window,commonly used NMR methods for investigatingμs-ms timescale dynamics include Carr-Purcell-Meiboom-Gill(CPMG)relaxation dispersion,chemical exchange saturation transfer(CEST),and rotating-frame longitudinal relaxation dispersion(R_(1ρ)relaxation dispersion).This review provides a brief ove rview of the fundamental principles and some recent advances of these methods,highlighting their interrelationships and applications in elucidating biomolecular dynamics.展开更多
基金the National Natural Science Foundation of China(61671228,61728107)
文摘本文通过比较 7 T 场强下化学交换饱和转移(chemical exchange saturation transfer,CEST)成像技术不同量化方式在急性帕金森氏病小鼠模型研究中的应用效果,探讨了客观无创的帕金森氏病研究方案.使用 Bruker PharmaScan7 T小动物磁共振成像(Magnetic Resonance Imaging,MRI)扫描仪,对经 1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)急性造模前及造模后第3、10天的小鼠黑质、皮层及海马进行扫描,计算弛豫时间 T1、T2、MTRasym(magnetization transfer ratio based on asymmetry analysis)、MTRrex(magnetization transfer ratio yielding Rex)、AREX(apparent exchange-dependent relaxation)及5池拟合后的胺峰面积 Areaamine、酰胺峰面积 Areaamide.结果显示仅黑质中融合了倒Z谱分析和5池洛仑兹拟合所得的量化指标 MTRrex、AREX及Areaamine在造模后显著减小,与黑质免疫组化结果一致,而 T1、T2以及基于Z谱非对称性分析的 MTRasym未见统计学差异,这表明此量化方式消除了直接饱和效应及磁化转移效应的影响,准确性上要优于Z谱非对称分析法,更能正确地提示帕金森氏病黑质的变化.
基金supported under the National Natural Science Foundation of China(Nos.22077123 and 21977099)。
文摘Nuclear magnetic resonance(NMR)spectroscopy has provided many powerful tools for the study of dynamic processes.Among the reported methods,chemical exchange saturation transfer(CEST)is more suitable for systems with slow exchange rates,and there will be promising in the detection and dynamic mechanism of metastable substances.It has been widely used in magnetic resonance imaging(MRI),however whether it is applicable in the field of chemical kinetics needs more examples.Here we studied,as a proof of concept,the kinetics of the slow chemical exchange between the two N-methyl protons of N,N-dimethylacetylamide(DMA),exploiting QUantifying Exchange using Z-spectrum(QUEZS)and QUantifying Exchange using Saturation Time(QUEST)methods.It turned out that both of QUEZS and QUEST could give the corresponding exchange rates,showcasing the capability of this method to provide accurate kinetic data under a range of temperatures.Our results clearly demonstrated the reliability of CEST-based techniques as a tool for dynamic kinetics by NMR.
文摘Diamagnetic CEST(diaCEST)MRI contrast agents(CAs)have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters,even after the agent is administered.However,the low efficiency and small solute−solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications.Low efficiency demands high dosage,while small offset invites unwanted interference from the endogenous metabolites present in the human body.So far,the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate.Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA.It was recently shown that hydrothermally synthesized carbon nanodots(CDs)have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs.Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute−solvent offset and contrast efficiency.In particular,we demonstrate 300%enhancement in offset and 100%enhancement in efficiency following the formation of carbon-dots from a urea−citric acid mixture.
基金financially supported by funds from the Natural Science Foundation of Beijing Municipality(Grant Number 7232251)the National Natural Science Foundation of China(Grant Number 22474006)。
文摘The dynamics of biomolecules span across a wide range of timescales,reflecting the complexity of free energy landscapes of biomolecules.Among these,the microsecond-tomillisecond(μs-ms)timescale dynamics are particularly significant,offering detailed insights into the kinetic,thermodynamic,and structural aspects of biological function.Many critical biological processes,including enzyme catalysis,protein folding,ligand binding,and allosteric regulation,operate within this timescale.Nuclear magnetic resonance(NMR)spectroscopy is a powerful technique for probing molecular dynamics in this time window,commonly used NMR methods for investigatingμs-ms timescale dynamics include Carr-Purcell-Meiboom-Gill(CPMG)relaxation dispersion,chemical exchange saturation transfer(CEST),and rotating-frame longitudinal relaxation dispersion(R_(1ρ)relaxation dispersion).This review provides a brief ove rview of the fundamental principles and some recent advances of these methods,highlighting their interrelationships and applications in elucidating biomolecular dynamics.
