Imaging Contrast

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Guanshu Liu - One of the best experts on this subject based on the ideXlab platform.

  • triazoles as t2 exchange magnetic resonance Imaging Contrast agents for the detection of nitrilase activity
    Chemistry: A European Journal, 2018
    Co-Authors: Jia Zhang, Zheng Han, Xuhe Liao, Peter C M Van Zijl, Xing Yang, Guanshu Liu
    Abstract:

    We characterized the T2 -exchange (T2ex ) magnetic resonance Imaging (MRI) Contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T2ex Contrast agents, with an optimal exchange-based relaxivity r2ex of 0.10 s-1  mm-1 at physiological pH and B0 =9.4 T. A fit of r2ex data to the Swift-Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r2ex was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T2ex MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R2ex . Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.

  • Imaging in vivo extracellular ph with a single paramagnetic chemical exchange saturation transfer magnetic resonance Imaging Contrast agent
    Molecular Imaging, 2012
    Co-Authors: Guanshu Liu, Vipul R Sheth, Mark D Pagel
    Abstract:

    The measurement of extracellular pH (pHe) has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance Imaging (MRI) c...

  • monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance Imaging Contrast agent
    Journal of the American Chemical Society, 2011
    Co-Authors: Guanshu Liu, Yajie Liang, Amnon Barshir, Kannie W Y Chan, Chulani Galpoththawela, Segun M Bernard, Terence Tse, Nirbhay N Yadav, Piotr Walczak
    Abstract:

    Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance Imaging (MRI) Contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST Imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after ...

  • using two chemical exchange saturation transfer magnetic resonance Imaging Contrast agents for molecular Imaging studies
    Accounts of Chemical Research, 2009
    Co-Authors: Meser M Ali, Guanshu Liu, Tejas Shah, Christopher A Flask, Mark D Pagel
    Abstract:

    Responsive magnetic resonance Imaging (MRI) Contrast agents can change MR image Contrast in response to a molecular biomarker. Quantitative detection of the biomarker requires an accounting of the other effects that may alter MR image Contrast, such as a change in the agent’s concentration, magnetic field variations, and hardware sensitivity profiles. A second unresponsive MRI Contrast agent may serve as an “internal control” to isolate the detection of the molecular biomarker. Chemical exchange saturation transfer (CEST) MRI Contrast agents can be selectively detected, providing the opportunity to combine a responsive CEST agent and an unresponsive CEST agent during the same MRI scan session. When two CEST MRI Contrast agents are used for molecular Imaging applications, the CEST agents should be designed to maximize accurate quantification of the concentrations of the two agents. From a chemical perspective, CEST agents behave like enzymes that catalyze the conversion of an unsaturated water “substrate” ...

Mark D Pagel - One of the best experts on this subject based on the ideXlab platform.

Nirbhay N Yadav - One of the best experts on this subject based on the ideXlab platform.

  • phenols as diamagnetic t2 exchange magnetic resonance Imaging Contrast agents
    Chemistry: A European Journal, 2018
    Co-Authors: Jia Zhang, Peter C M Van Zijl, Nirbhay N Yadav, Stephanie Slania, Jing Liu, Rongfu Wang, Jianhua Zhang, Martin G Pomper
    Abstract:

    Although T2 -exchange (T2ex ) NMR phenomena have been known for decades, there has been a resurgence of interest to develop T2ex MRI Contrast agents. One indispensable advantage of T2ex MR agents is the possibility of using non-toxic and/or bio-compatible diamagnetic compounds with intermediate exchangeable protons. Herein a library of phenol-based compounds is screened and their T2ex Contrast (exchange relaxivity, r2ex ) at 9.4 T determined. The T2ex Contrast of phenol protons allows direct detection by MRI at a millimolar concentration level. The effect of chemical modification of the phenol on the T2ex MRI Contrast through modulation of exchange rate and chemical shift was also studied and provides a guideline for use of endogenous and exogenous phenols for T2ex MRI Contrast. As a proof-of-principle application, phenol T2ex Contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.

  • monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance Imaging Contrast agent
    Journal of the American Chemical Society, 2011
    Co-Authors: Guanshu Liu, Yajie Liang, Amnon Barshir, Kannie W Y Chan, Chulani Galpoththawela, Segun M Bernard, Terence Tse, Nirbhay N Yadav, Piotr Walczak
    Abstract:

    Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance Imaging (MRI) Contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST Imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after ...

  • monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance Imaging Contrast agent
    Journal of the American Chemical Society, 2011
    Co-Authors: Yajie Liang, Amnon Barshir, Kannie W Y Chan, Chulani Galpoththawela, Segun M Bernard, Nirbhay N Yadav, Piotr Walczak, Michael T Mcmahon, Jeff W M Bulte
    Abstract:

    Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance Imaging (MRI) Contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST Imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after deamination by recombinant CDase, the CEST Contrast disappears. In addition, expression of the enzyme in three different cell lines exhibiting different expression levels of CDase shows good agreement with the CDase activity measured with CEST MRI. Consequently, CDase activity was imaged with high-resolution CEST MRI. These data demonstrate the ability to detect enzyme activity based on proton exchange. Consequently, CEST MRI has the potential to follow the kinetics of multiple enzymes in real time in living tissue.

Jeff W M Bulte - One of the best experts on this subject based on the ideXlab platform.

  • monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance Imaging Contrast agent
    Journal of the American Chemical Society, 2011
    Co-Authors: Yajie Liang, Amnon Barshir, Kannie W Y Chan, Chulani Galpoththawela, Segun M Bernard, Nirbhay N Yadav, Piotr Walczak, Michael T Mcmahon, Jeff W M Bulte
    Abstract:

    Chemical exchange saturation transfer (CEST) is a new approach for generating magnetic resonance Imaging (MRI) Contrast that allows monitoring of protein properties in vivo. In this method, a radiofrequency pulse is used to saturate the magnetization of specific protons on a target molecule, which is then transferred to water protons via chemical exchange and detected using MRI. One advantage of CEST Imaging is that the magnetizations of different protons can be specifically saturated at different resonance frequencies. This enables the detection of multiple targets simultaneously in living tissue. We present here a CEST MRI approach for detecting the activity of cytosine deaminase (CDase), an enzyme that catalyzes the deamination of cytosine to uracil. Our findings suggest that metabolism of two substrates of the enzyme, cytosine and 5-fluorocytosine (5FC), can be detected using saturation pulses targeted specifically to protons at +2 ppm and +2.4 ppm (with respect to water), respectively. Indeed, after deamination by recombinant CDase, the CEST Contrast disappears. In addition, expression of the enzyme in three different cell lines exhibiting different expression levels of CDase shows good agreement with the CDase activity measured with CEST MRI. Consequently, CDase activity was imaged with high-resolution CEST MRI. These data demonstrate the ability to detect enzyme activity based on proton exchange. Consequently, CEST MRI has the potential to follow the kinetics of multiple enzymes in real time in living tissue.

  • improved molecular Imaging Contrast agent for detection of human thrombus
    Magnetic Resonance in Medicine, 2003
    Co-Authors: Patrick M Winter, Shelton D Caruthers, Xin Yu, Shengkwei Song, Junjie Chen, Brad Miller, Jeff W M Bulte, David J Robertson
    Abstract:

    Molecular Imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular Imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bis-oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPA-phosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion- and particle-based r1 relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM)-1 and 2.48 × 106 (s*mM)-1, respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% ± 5% higher change in R1 values at 1.5 T (ΔR1 = 0.77 ± 0.02 1/s) relative to Gd-DTPA-BOA (ΔR1 = 0.45 ± 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular Imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack. Magn Reson Med 50:411–416, 2003. © 2003 Wiley-Liss, Inc.

Peter C M Van Zijl - One of the best experts on this subject based on the ideXlab platform.

  • triazoles as t2 exchange magnetic resonance Imaging Contrast agents for the detection of nitrilase activity
    Chemistry: A European Journal, 2018
    Co-Authors: Jia Zhang, Zheng Han, Xuhe Liao, Peter C M Van Zijl, Xing Yang, Guanshu Liu
    Abstract:

    We characterized the T2 -exchange (T2ex ) magnetic resonance Imaging (MRI) Contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T2ex Contrast agents, with an optimal exchange-based relaxivity r2ex of 0.10 s-1  mm-1 at physiological pH and B0 =9.4 T. A fit of r2ex data to the Swift-Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r2ex was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T2ex MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R2ex . Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.

  • phenols as diamagnetic t2 exchange magnetic resonance Imaging Contrast agents
    Chemistry: A European Journal, 2018
    Co-Authors: Jia Zhang, Peter C M Van Zijl, Nirbhay N Yadav, Stephanie Slania, Jing Liu, Rongfu Wang, Jianhua Zhang, Martin G Pomper
    Abstract:

    Although T2 -exchange (T2ex ) NMR phenomena have been known for decades, there has been a resurgence of interest to develop T2ex MRI Contrast agents. One indispensable advantage of T2ex MR agents is the possibility of using non-toxic and/or bio-compatible diamagnetic compounds with intermediate exchangeable protons. Herein a library of phenol-based compounds is screened and their T2ex Contrast (exchange relaxivity, r2ex ) at 9.4 T determined. The T2ex Contrast of phenol protons allows direct detection by MRI at a millimolar concentration level. The effect of chemical modification of the phenol on the T2ex MRI Contrast through modulation of exchange rate and chemical shift was also studied and provides a guideline for use of endogenous and exogenous phenols for T2ex MRI Contrast. As a proof-of-principle application, phenol T2ex Contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.