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
Objective This study aims to explore the clinical applicability and relevance of giycosaminoglycan Chemical Exchange Saturation Transfer （gagCEST） for intervertebral disc. Methods 25 subjects ranging in age from 24 ...Objective This study aims to explore the clinical applicability and relevance of giycosaminoglycan Chemical Exchange Saturation Transfer （gagCEST） for intervertebral disc. Methods 25 subjects ranging in age from 24 yrs to 74 yrs were enrolled, gagCEST was acquired using a single-slice TSE sequence on a 3T. Saturation used a continuous rectangular RF pulse with B1=0.8 I^T and a fixed duration time =1100 ms. Sagittal image was obtained firstly without saturation pulse, and then saturated images were acquired at 52 offsets ranging from ＋0.i25 to ＋_7 parts per million （ppm）. MR T2 relaxivity map was acquired at the identical location. Six subjects were scanned twice to assess scan-rescan reproducibility. Results GagCEST intraclass correlation coefficient （ICC） of six subjects was 0.759 for nucleus pulposus （NP） and 0.508 for annulus fibrosus （AF）. Bland-Altman plots showed NP had a mean difference of 0.10% （95% limits of agreement： -3.02% to 3.22%）; while that of AF was 0.34% （95% limits of agreement： -2.28% to 2.95%）. For the 25 subjects, gag CEST in NP decreased as disc degeneration increased, with a similar trend to T2 relaxivity. Gag CEST of AF showed a better correlation with disc degeneration than T2 relaxivity. Conclusion GagCEST in NP and AF decreased as disc degeneration increased, while gagCEST in AF showed a better correlation than T2 relaxivity.展开更多
Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in p...Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in proteins can be classified as coherent(via dipolar spin diffusion)and incoherent(via chemical exchange and nuclear Overhauser effect)transfers.Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of'H polarization transfers from water to the proteins.These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually.Here,we review water-protein polarization transfer techniques in solid state NMR with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins.The measurements of the pure chemical exchange ki-netics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane bound species at the water-bilayer interface.In addi-tion,the perspective of chemical exchange saturation transfer(CEST)experiments in membrane-bound proteins/peptides is further discussed.展开更多
The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch-McConnell equations describing the behavior of magnetization in magnetic resonance imaging (MRI) in the presen...The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch-McConnell equations describing the behavior of magnetization in magnetic resonance imaging (MRI) in the presence of multiple chemical exchange pools. First, the time-dependent Bloch- McConnell equations were reduced to a homogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation and Kronecker tensor product. From these solutions, the longitudinal relaxation rate (R1ρ) and transverse relaxation rate in the rotating frame (R2ρ) and Z-spectra were obtained. As illustrative examples, the numerical solutions for linear and star-type three-pool chemical exchange models and linear, star- type, and kite-type four-pool chemical exchange models were presented. The effects of saturation time (ST) and radiofrequency irradiation power (ω1) on the chemical exchange saturation transfer (CEST) effect in these models were also investigated. Although R1ρ and R2ρ were not affected by the ST, the CEST effect observed in the Z-spectra increased and saturated with increasing ST. When ω1 was varied, the CEST effect increased with increasing ω1 in R1ρ, R2ρ, and Z-spectra. When ω1 was large, however, the spillover effect due to the direct saturation of bulk water protons also increased, suggesting that these parameters must be determined in consideration of both the CEST and spillover effects. Our method will be useful for analyzing the complex CEST contrast mechanism and for investigating the optimal conditions for CEST MRI in the presence of multiple chemical exchange pools.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
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partially by grants from the Research Grants Council of the Hong Kong SAR,China(Project No.SEG_CUHK02)
文摘Objective This study aims to explore the clinical applicability and relevance of giycosaminoglycan Chemical Exchange Saturation Transfer （gagCEST） for intervertebral disc. Methods 25 subjects ranging in age from 24 yrs to 74 yrs were enrolled, gagCEST was acquired using a single-slice TSE sequence on a 3T. Saturation used a continuous rectangular RF pulse with B1=0.8 I^T and a fixed duration time =1100 ms. Sagittal image was obtained firstly without saturation pulse, and then saturated images were acquired at 52 offsets ranging from ＋0.i25 to ＋_7 parts per million （ppm）. MR T2 relaxivity map was acquired at the identical location. Six subjects were scanned twice to assess scan-rescan reproducibility. Results GagCEST intraclass correlation coefficient （ICC） of six subjects was 0.759 for nucleus pulposus （NP） and 0.508 for annulus fibrosus （AF）. Bland-Altman plots showed NP had a mean difference of 0.10% （95% limits of agreement： -3.02% to 3.22%）; while that of AF was 0.34% （95% limits of agreement： -2.28% to 2.95%）. For the 25 subjects, gag CEST in NP decreased as disc degeneration increased, with a similar trend to T2 relaxivity. Gag CEST of AF showed a better correlation with disc degeneration than T2 relaxivity. Conclusion GagCEST in NP and AF decreased as disc degeneration increased, while gagCEST in AF showed a better correlation than T2 relaxivity.
基金This work was supported by NIH Grants AI023007 and GM122698All NMR experiments were carried out at the National High Magnetic Field lab(NHMFL)supported by the NSF Cooperative Agreement DMR-1644779 and the State of Florida.
文摘Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments.In general,the 1H polarization transfers berween water molecules and site--specific protons in proteins can be classified as coherent(via dipolar spin diffusion)and incoherent(via chemical exchange and nuclear Overhauser effect)transfers.Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of'H polarization transfers from water to the proteins.These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually.Here,we review water-protein polarization transfer techniques in solid state NMR with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins.The measurements of the pure chemical exchange ki-netics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane bound species at the water-bilayer interface.In addi-tion,the perspective of chemical exchange saturation transfer(CEST)experiments in membrane-bound proteins/peptides is further discussed.
文摘The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch-McConnell equations describing the behavior of magnetization in magnetic resonance imaging (MRI) in the presence of multiple chemical exchange pools. First, the time-dependent Bloch- McConnell equations were reduced to a homogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation and Kronecker tensor product. From these solutions, the longitudinal relaxation rate (R1ρ) and transverse relaxation rate in the rotating frame (R2ρ) and Z-spectra were obtained. As illustrative examples, the numerical solutions for linear and star-type three-pool chemical exchange models and linear, star- type, and kite-type four-pool chemical exchange models were presented. The effects of saturation time (ST) and radiofrequency irradiation power (ω1) on the chemical exchange saturation transfer (CEST) effect in these models were also investigated. Although R1ρ and R2ρ were not affected by the ST, the CEST effect observed in the Z-spectra increased and saturated with increasing ST. When ω1 was varied, the CEST effect increased with increasing ω1 in R1ρ, R2ρ, and Z-spectra. When ω1 was large, however, the spillover effect due to the direct saturation of bulk water protons also increased, suggesting that these parameters must be determined in consideration of both the CEST and spillover effects. Our method will be useful for analyzing the complex CEST contrast mechanism and for investigating the optimal conditions for CEST MRI in the presence of multiple chemical exchange pools.
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.
