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
Objective This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance im...Objective This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging(CEST-MRI).Methods Three sets of Z-spectrum data with saturation power(B_(1))values of 1.5,2.5,and 3.5µT,respectively,were acquired from 17 patients with ischemic stroke.Multiple contrasts contributing to the Z-spectrum,including fitted amide proton transfer(APT_(fitted)),+2 ppm peak(CEST@2ppm),concomitantly fitted APT_(fitted) and CEST@2ppm(APT&CEST@2ppm),semisolid magnetization transfer contrast(MT),aliphatic nuclear Overhauser effect(NOE),and direct saturation of water(DSW),were fitted with 4 and 5 Lorentzian functions,respectively.The CEST metrics were compared between ischemic lesions and contralateral normal white matter(CNWM),and the correlation between the CEST metrics and the apparent diffusion coefficient(ADC)was assessed.The differences in the Z-spectrum metrics under varied B1 values were also investigated.Results Ischemic lesions showed increased APTfitted,CEST@2ppm,APT&CEST@2ppm,NOE,and DSW as well as decreased MT.APT&CEST@2ppm,MT,and DSW showed a significant correlation with ADC[APT&CEST@2ppm at the 3 B_(1) values:R=0.584/0.467/0.551;MT at the 3 B_(1) values:R=−0.717/−0.695/−0.762(4-parameter fitting),R=−0.734/−0.711/−0.785(5-parameter fitting);DSW of 4-/5-parameter fitting:R=0.794/0.811(2.5µT),R=0.800/0.790(3.5µT)].However,the asymmetric analysis of amide proton transfer(APT_(asym))could not differentiate the lesions from CNWM and showed no correlation with ADC.Furthermore,the Z-spectrum contrasts varied with B_(1).Conclusion The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.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
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
The cation exchange and the chemical weathering are two important processes for sedi-ments to buffer the acidification of surface water. In this paper, for sediments these two processeshave been studied. The relations...The cation exchange and the chemical weathering are two important processes for sedi-ments to buffer the acidification of surface water. In this paper, for sediments these two processeshave been studied. The relationship between BFC of sediments and ANC of the surface waters andthe weathering characteristics of sediments were discussed. The buffering effect and mechanism of sedi-ments against acidic deposition have also been studied. The results show that BFC of sediments arepositively correlative to ANC of the surface waters. the chemical weathering rate of sediments can beexpressed as R=k×[H ̄ +] ̄m.展开更多
Biomedical imaging,especially molecular imaging,has been a driving force in scientific discovery,technological innovation,and precision medicine in the past two decades.While substantial advances and discoveries in ch...Biomedical imaging,especially molecular imaging,has been a driving force in scientific discovery,technological innovation,and precision medicine in the past two decades.While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers,translating these exogenous agents to clinical application in precision medicine is a major challenge.Among the clinically accepted imaging modalities,magnetic resonance imaging(MRI)and magnetic resonance spectroscopy(MRS)exemplify the most effective and robust biomedical imaging tools.Both MRI and MRS enable a broad range of chemical,biological diagnosis and characterization of many diseases and image-guided interventions.Using chemical,biological,and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules,label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases.This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery,preclinical investigation,and image-guided clinical management.Examples are provided to demonstrate strategies for using endogenous probes to report the molecular,metabolic,physiological,and functional events and processes in living systems,including patients.Future perspectives on label-free molecular MRI and its challenges as well as potential solutions,including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI,are discussed.展开更多
As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoreti...As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect(i.e. conjugation and hyper-conjugation effects) becomes important when the steric hindrance is insignificant.展开更多
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supported by grants from the Guangzhou General Guidance Project of Health Science and Technology(No.20231A011013)the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110737).
文摘Objective This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging(CEST-MRI).Methods Three sets of Z-spectrum data with saturation power(B_(1))values of 1.5,2.5,and 3.5µT,respectively,were acquired from 17 patients with ischemic stroke.Multiple contrasts contributing to the Z-spectrum,including fitted amide proton transfer(APT_(fitted)),+2 ppm peak(CEST@2ppm),concomitantly fitted APT_(fitted) and CEST@2ppm(APT&CEST@2ppm),semisolid magnetization transfer contrast(MT),aliphatic nuclear Overhauser effect(NOE),and direct saturation of water(DSW),were fitted with 4 and 5 Lorentzian functions,respectively.The CEST metrics were compared between ischemic lesions and contralateral normal white matter(CNWM),and the correlation between the CEST metrics and the apparent diffusion coefficient(ADC)was assessed.The differences in the Z-spectrum metrics under varied B1 values were also investigated.Results Ischemic lesions showed increased APTfitted,CEST@2ppm,APT&CEST@2ppm,NOE,and DSW as well as decreased MT.APT&CEST@2ppm,MT,and DSW showed a significant correlation with ADC[APT&CEST@2ppm at the 3 B_(1) values:R=0.584/0.467/0.551;MT at the 3 B_(1) values:R=−0.717/−0.695/−0.762(4-parameter fitting),R=−0.734/−0.711/−0.785(5-parameter fitting);DSW of 4-/5-parameter fitting:R=0.794/0.811(2.5µT),R=0.800/0.790(3.5µT)].However,the asymmetric analysis of amide proton transfer(APT_(asym))could not differentiate the lesions from CNWM and showed no correlation with ADC.Furthermore,the Z-spectrum contrasts varied with B_(1).Conclusion The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.
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.
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The cation exchange and the chemical weathering are two important processes for sedi-ments to buffer the acidification of surface water. In this paper, for sediments these two processeshave been studied. The relationship between BFC of sediments and ANC of the surface waters andthe weathering characteristics of sediments were discussed. The buffering effect and mechanism of sedi-ments against acidic deposition have also been studied. The results show that BFC of sediments arepositively correlative to ANC of the surface waters. the chemical weathering rate of sediments can beexpressed as R=k×[H ̄ +] ̄m.
基金supported in parts by the grants from NIH(R01CA203388−04,R01AG067736−02)to HM,(R01CA261974,R33HL161756)to GL.CCF is supported,in part,by NIH grant DP2NS127704−01.
文摘Biomedical imaging,especially molecular imaging,has been a driving force in scientific discovery,technological innovation,and precision medicine in the past two decades.While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers,translating these exogenous agents to clinical application in precision medicine is a major challenge.Among the clinically accepted imaging modalities,magnetic resonance imaging(MRI)and magnetic resonance spectroscopy(MRS)exemplify the most effective and robust biomedical imaging tools.Both MRI and MRS enable a broad range of chemical,biological diagnosis and characterization of many diseases and image-guided interventions.Using chemical,biological,and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules,label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases.This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery,preclinical investigation,and image-guided clinical management.Examples are provided to demonstrate strategies for using endogenous probes to report the molecular,metabolic,physiological,and functional events and processes in living systems,including patients.Future perspectives on label-free molecular MRI and its challenges as well as potential solutions,including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI,are discussed.
基金NSFC (No. 21202006)FRFCU (No. FRF-TP14-015A2) for financial supports and Super-computer Center of Shanghai and Shenzhen for technical supports
文摘As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect(i.e. conjugation and hyper-conjugation effects) becomes important when the steric hindrance is insignificant.