Saturation Transfer

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

  • carbon dots as a new class of diamagnetic chemical exchange Saturation Transfer diacest mri contrast agents
    Angewandte Chemie, 2019
    Co-Authors: Jia Zhang, Jeff W M Bulte, Peter C M Van Zijl, Zheng Han, Yue Yuan, Minling Gao, Chengyan Chu, Mingyao Ying
    Abstract:

    While carbon dots (C-dots) have been extensively investigated pertaining to their fluorescent, phosphorescent, electrochemiluminescent, optoelectronic, and catalytic features, their inherent chemical exchange Saturation Transfer magnetic resonance imaging (CEST MRI) properties are unknown. By virtue of their hydrophilicity and abundant exchangeable protons of hydroxyl, amine, and amide anchored on the surface, we report here that C-dots can be adapted as effective diamagnetic CEST (diaCEST) MRI contrast agents. As a proof-of-concept demonstration, human glioma cells were labeled with liposomes with or without encapsulated C-dots and implanted in mouse brain. In vivo CEST MRI was able to clearly differentiate labeled cells from non-labeled cells. The present findings may encourage new applications of C-dots for in vivo imaging in deep tissues, which is currently not possible using conventional fluorescent (near-infrared) C-dots.

  • extradomain b fibronectin targeted dextran based chemical exchange Saturation Transfer magnetic resonance imaging probe for detecting pancreatic cancer
    Bioconjugate Chemistry, 2019
    Co-Authors: Peter C M Van Zijl, Zheng Han, Shuixing Zhang, Kenji Fujiwara, Jia Zhang, Jing Liu, Lei Zheng
    Abstract:

    A dextran-peptide conjugate was developed for magnetic resonance (MR) molecular imaging of pancreatic ductal adenocarcinoma (PDAC) through its overexpressed microenvironment biomarker, extradomain-B fibronectin (EDB-FN). This new agent consists of diamagnetic and biocompatible dextran and a targeting peptide. Dextrans can be directly detected by chemical exchange Saturation Transfer magnetic resonance imaging (CEST MRI) without the need for radionuclide or metallic labeling. In addition, large molecular weight dextran, dextran 10 (MW ∼ 10 kDa), provides an approximately 50 times higher sensitivity per molecule than a single glucose unit. The potential of this highly biocompatible diamagnetic probe is demonstrated in a murine syngeneic allograft PDAC tumor model. The biocompatibility and sensitivity of this new agent clearly show potential for a path to clinical translation.

  • Extradomain‑B Fibronectin-Targeted Dextran-Based Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Probe for Detecting Pancreatic Cancer
    2019
    Co-Authors: Zheng Han, Peter C M Van Zijl, Shuixing Zhang, Kenji Fujiwara, Jia Zhang, Jing Liu, Lei Zheng, Guanshu Liu
    Abstract:

    A dextran-peptide conjugate was developed for magnetic resonance (MR) molecular imaging of pancreatic ductal adenocarcinoma (PDAC) through its overexpressed microenvironment biomarker, extradomain-B fibronectin (EDB-FN). This new agent consists of diamagnetic and biocompatible dextran and a targeting peptide. Dextrans can be directly detected by chemical exchange Saturation Transfer magnetic resonance imaging (CEST MRI) without the need for radionuclide or metallic labeling. In addition, large molecular weight dextran, dextran 10 (MW ∼ 10 kDa), provides an approximately 50 times higher sensitivity per molecule than a single glucose unit. The potential of this highly biocompatible diamagnetic probe is demonstrated in a murine syngeneic allograft PDAC tumor model. The biocompatibility and sensitivity of this new agent clearly show potential for a path to clinical translation

  • magnetization Transfer contrast and chemical exchange Saturation Transfer mri features and analysis of the field dependent Saturation spectrum
    NeuroImage, 2018
    Co-Authors: Peter C M Van Zijl, Gregory J Stanisz, Linda Knutsson, Wilfred W Lam
    Abstract:

    Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the Transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss (“Saturation”). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these Saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum. In tissue, these Z-spectra contain the convolution of multiple Saturation Transfer effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange contributions from protons in semi-solid and mobile macromolecules or tissue metabolites. As a consequence, their appearance depends on the magnetic field strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and length, and interpulse delay, which presents a major problem for quantification and reproducibility of MTC and CEST effects. The use of higher B0 can bring several advantages. In addition to higher detection sensitivity (signal-to-noise ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the Saturation Transferred to water to be retained longer. While MTC studies are non-specific at any field strength, CEST specificity is expected to increase at higher field because of a larger chemical shift dispersion of the resonances of interest (similar to MRS). In addition, shifting to a slower exchange regime at higher B0 facilitates improved detection of the guanidinium protons of creatine and the inherently broad resonances of the amine protons in glutamate and the hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due to the higher mobility of the contributing protons in CEST versus MTC, many new pulse sequences can be designed to more specifically edit for CEST signals and to remove MTC contributions.

  • variable delay multi pulse train for fast chemical exchange Saturation Transfer and relayed nuclear overhauser enhancement mri
    Magnetic Resonance in Medicine, 2014
    Co-Authors: Nirbhay N Yadav, Michael T Mcmahon, Kannie W Y Chan, Piotr Walczak, Amnon Barshir, Craig K Jones, Jiangyang Zhang, Peter C M Van Zijl
    Abstract:

    Purpose Chemical exchange Saturation Transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. Methods The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency Saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of Saturation Transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water Saturation and, when using low radiofrequency power, minimal magnetization Transfer contrast interference. Results When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization Transfer processes (rate < 100–150 Hz), such as amide proton Transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. Conclusions VDMP-CEST provides an approach to detect CEST effect by sensitizing Saturation experiments to slower exchange processes without interference of direct water Saturation and without need to acquire Z-spectra and perform asymmetry analysis. Magn Reson Med 71:1798–1812, 2014. © 2013 Wiley Periodicals, Inc.

Phillip Zhe Sun - One of the best experts on this subject based on the ideXlab platform.

  • renal ph imaging using chemical exchange Saturation Transfer cest mri basic concept
    Methods of Molecular Biology, 2021
    Co-Authors: Dario Livio Longo, Michael T Mcmahon, Phillip Zhe Sun, Pietro Irrera, Lorena Consolino
    Abstract:

    Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange Saturation Transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

  • analysis protocol for the quantification of renal ph using chemical exchange Saturation Transfer cest mri
    Methods of Molecular Biology, 2021
    Co-Authors: Hahnsung Kim, Michael T Mcmahon, Dario Livio Longo, Daisy Villano, Phillip Zhe Sun
    Abstract:

    The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange Saturation Transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.

  • a generalized ratiometric chemical exchange Saturation Transfer cest mri approach for mapping renal ph using iopamidol
    Magnetic Resonance in Medicine, 2018
    Co-Authors: Iris Y Zhou, Dario Livio Longo, Takahiro Igarashi, Silvio Aime, Phillip Zhe Sun
    Abstract:

    PURPOSE To extend the pH detection range of iopamidol-based ratiometric chemical exchange Saturation Transfer (CEST) MRI at sub-high magnetic field and establish quantitative renal pH MRI. METHODS Chemical exchange Saturation Transfer imaging was performed on iopamidol phantoms with pH of 5.5 to 8.0 and in vivo on rat kidneys (n = 5) during iopamidol administration at a 4.7 T. Iopamidol CEST effects were described using a multipool Lorentzian model. A generalized ratiometric analysis was conducted by ratioing resolved iopamidol CEST effects at 4.3 and 5.5 ppm obtained under 1.0 and 2.0 µT, respectively. The pH detection range was established for both the standard ratiometric analysis and the proposed resolved approach. Renal pH was mapped in vivo with regional pH assessed by one-way analysis of variance. RESULTS Good-fitting performance was observed in multipool Lorentzian resolving of CEST effects (R2 s > 0.99). The proposed approach extends the in vitro pH detection range to 5.5 to 7.5 at 4.7 T. In vivo renal pH was measured to be 7.0 ± 0.1, 6.8 ± 0.1, and 6.5 ± 0.2 for cortex, medulla and calyx, respectively (P < 0.05). CONCLUSIONS The proposed ratiometric approach extended the iopamidol pH detection range, enabling the renal pH mapping in vivo, which is promising for pH imaging studies at sub-high or low fields with potential clinical applicability. Magn Reson Med 79:1553-1558, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  • progress toward quantitative in vivo chemical exchange Saturation Transfer cest mri
    Israel Journal of Chemistry, 2017
    Co-Authors: Iris Y Zhou, Bensheng Qiu, Phillip Zhe Sun
    Abstract:

    Chemical exchange Saturation Transfer (CEST) MRI provides a sensitive detection mechanism for imaging dilute labile protons, complementing the routine radiological exams. Enormous progress has been achieved in CEST MRI and image analysis, from the mathematical modeling, CEST agent design, and most importantly, increasing adoption of CEST imaging in the clinical setting. Therefore, CEST imaging represents an emerging field that involves multiple disciplines and together made a remarkable transition from the simplistic CEST-weighted MRI to quantitative CEST (qCEST) analysis. This review focuses on the recent advancements in CEST quantification techniques and findings of in vivo CEST imaging in representative disorders of ischemia, tumor, and epilepsy. In addition, limitations of current CEST methodologies are examined that should help guide future development of more sensitive and quantitative CEST imaging techniques and ultimately, facilitate their adoption in the clinical setting.

  • tissue characterization with quantitative high resolution magic angle spinning chemical exchange Saturation Transfer z spectroscopy
    Analytical Chemistry, 2016
    Co-Authors: Iris Y Zhou, Takahiro Igarashi, Taylor L Fuss, Weiping Jiang, Xin Zhou, Leo L Cheng, Phillip Zhe Sun
    Abstract:

    Chemical exchange Saturation Transfer (CEST) provides sensitive magnetic resonance (MR) contrast for probing dilute compounds via exchangeable protons, serving as an emerging molecular imaging methodology. CEST Z-spectrum is often acquired by sweeping radiofrequency Saturation around bulk water resonance, offset by offset, to detect CEST effects at characteristic chemical shift offsets, which requires prolonged acquisition time. Herein, combining high-resolution magic angle spinning (HRMAS) with concurrent application of gradient and rf Saturation to achieve fast Z-spectral acquisition, we demonstrated the feasibility of fast quantitative HRMAS CEST Z-spectroscopy. The concept was validated with phantoms, which showed excellent agreement with results obtained from conventional HRMAS MR spectroscopy (MRS). We further utilized the HRMAS Z-spectroscopy for fast ex vivo quantification of ischemic injury with rodent brain tissues after ischemic stroke. This method allows rapid and quantitative CEST characteriz...

Michael T Mcmahon - One of the best experts on this subject based on the ideXlab platform.

  • renal ph imaging using chemical exchange Saturation Transfer cest mri basic concept
    Methods of Molecular Biology, 2021
    Co-Authors: Dario Livio Longo, Michael T Mcmahon, Phillip Zhe Sun, Pietro Irrera, Lorena Consolino
    Abstract:

    Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange Saturation Transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

  • analysis protocol for the quantification of renal ph using chemical exchange Saturation Transfer cest mri
    Methods of Molecular Biology, 2021
    Co-Authors: Hahnsung Kim, Michael T Mcmahon, Dario Livio Longo, Daisy Villano, Phillip Zhe Sun
    Abstract:

    The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange Saturation Transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.

  • variable delay multi pulse train for fast chemical exchange Saturation Transfer and relayed nuclear overhauser enhancement mri
    Magnetic Resonance in Medicine, 2014
    Co-Authors: Nirbhay N Yadav, Michael T Mcmahon, Kannie W Y Chan, Piotr Walczak, Amnon Barshir, Craig K Jones, Jiangyang Zhang, Peter C M Van Zijl
    Abstract:

    Purpose Chemical exchange Saturation Transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. Methods The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency Saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of Saturation Transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water Saturation and, when using low radiofrequency power, minimal magnetization Transfer contrast interference. Results When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization Transfer processes (rate < 100–150 Hz), such as amide proton Transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. Conclusions VDMP-CEST provides an approach to detect CEST effect by sensitizing Saturation experiments to slower exchange processes without interference of direct water Saturation and without need to acquire Z-spectra and perform asymmetry analysis. Magn Reson Med 71:1798–1812, 2014. © 2013 Wiley Periodicals, Inc.

  • nuts and bolts of chemical exchange Saturation Transfer mri
    NMR in Biomedicine, 2013
    Co-Authors: Guanshu Liu, Michael T Mcmahon, Kannie W Y Chan, Xiaolei Song
    Abstract:

    Chemical exchange Saturation Transfer (CEST) has emerged as a novel MRI contrast mechanism that is well suited for molecular imaging studies. This new mechanism can be used to detect small amounts of contrast agent through the Saturation of rapidly exchanging protons on these agents, allowing a wide range of applications. CEST technology has a number of indispensable features, such as the possibility of simultaneous detection of multiple 'colors' of agents and of changes in their environment (e.g. pH, metabolites, etc.) through MR contrast. Currently, a large number of new imaging schemes and techniques are being developed to improve the temporal resolution and specificity and to correct for the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the last decade are summarized with the different imaging strategies and post-processing methods discussed from a practical point of view, including the description of their relative merits for the detection of CEST agents. The goal of the present work is to provide the reader with a fundamental understanding of the techniques developed, and to provide guidance to help refine future applications of this technology. This review is organized into three main sections ('Basics of CEST contrast', 'Implementation' and 'Post-processing'), and also includes a brief Introduction and Summary. The 'Basics of CEST contrast' section contains a description of the relevant background theory for Saturation Transfer and frequency-labeled Transfer, and a brief discussion of methods to determine exchange rates. The 'Implementation' section contains a description of the practical considerations in conducting CEST MRI studies, including the choice of magnetic field, pulse sequence, Saturation pulse, imaging scheme, and strategies to separate magnetization Transfer and CEST. The 'Post-processing' section contains a description of the typical image processing employed for B0 /B1 correction, Z-spectral interpolation, frequency-selective detection and improvement of CEST contrast maps.

  • high throughput screening of chemical exchange Saturation Transfer mr contrast agents
    Contrast Media & Molecular Imaging, 2010
    Co-Authors: Guanshu Liu, Assaf A Gilad, Jeff W M Bulte, Peter C M Van Zijl, Michael T Mcmahon
    Abstract:

    A new high-throughput MRI method for screening chemical exchange Saturation Transfer (CEST) agents is demonstrated, allowing simultaneous testing of multiple samples with minimal attention to sample configuration and shimming of the main magnetic field (B0). This approach, which is applicable to diamagnetic, paramagnetic and liposome CEST agents, employs a set of inexpensive glass or plastic capillary tubes containing CEST agents put together in a cheap plastic tube holder, without the need for liquid between the tubes to reduce magnetic susceptibility effects. In this setup, a reference image of direct water Saturation spectra is acquired in order to map the absolute water frequency for each volume element (voxel) in the sample image, followed by an image of Saturation Transfer spectra to determine the CEST properties. Even though the field over the total sample is very inhomogeneous due to air–tube interfaces, the shape of the direct Saturation spectra is not affected, allowing removal of susceptibility shift effects from the CEST data by using the absolute water frequencies from the reference map. As a result, quantitative information such as the mean CEST intensity for each sample can be extracted for multiple CEST agents at once. As an initial application, we demonstrate rapid screening of a library of 16 polypeptides for their CEST properties, but in principle the number of tubes is limited only by the available signal-noise-ratio, field of view and gradient strength for imaging. Copyright © 2010 John Wiley & Sons, Ltd.

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

  • Extradomain‑B Fibronectin-Targeted Dextran-Based Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Probe for Detecting Pancreatic Cancer
    2019
    Co-Authors: Zheng Han, Peter C M Van Zijl, Shuixing Zhang, Kenji Fujiwara, Jia Zhang, Jing Liu, Lei Zheng, Guanshu Liu
    Abstract:

    A dextran-peptide conjugate was developed for magnetic resonance (MR) molecular imaging of pancreatic ductal adenocarcinoma (PDAC) through its overexpressed microenvironment biomarker, extradomain-B fibronectin (EDB-FN). This new agent consists of diamagnetic and biocompatible dextran and a targeting peptide. Dextrans can be directly detected by chemical exchange Saturation Transfer magnetic resonance imaging (CEST MRI) without the need for radionuclide or metallic labeling. In addition, large molecular weight dextran, dextran 10 (MW ∼ 10 kDa), provides an approximately 50 times higher sensitivity per molecule than a single glucose unit. The potential of this highly biocompatible diamagnetic probe is demonstrated in a murine syngeneic allograft PDAC tumor model. The biocompatibility and sensitivity of this new agent clearly show potential for a path to clinical translation

  • metal ion sensing using ion chemical exchange Saturation Transfer 19f magnetic resonance imaging
    Journal of the American Chemical Society, 2013
    Co-Authors: Amnon Barshir, Guanshu Liu, Assaf A Gilad, Peter C M Van Zijl, Kannie W Y Chan, Jeff W M Bulte
    Abstract:

    Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca2+ in which the amplification strategy of chemical exchange Saturation Transfer (CEST) is combined with the broad range of chemical shifts found in 19F NMR spectroscopy to obtain magnetic resonance images of Ca2+. We exploited the chemical shift change (Δω) of 19F upon binding of Ca2+ to the 5,5′-difluoro derivative of 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (5F-BAPTA) by radiofrequency labeling at the Ca2+-bound 19F frequency and detection of the label Transfer to the Ca2+-free 19F frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca2+ onto free 5F-BAPTA and thus indirectly detect low Ca2+ concentrations with high sensitivity.

  • nuts and bolts of chemical exchange Saturation Transfer mri
    NMR in Biomedicine, 2013
    Co-Authors: Guanshu Liu, Michael T Mcmahon, Kannie W Y Chan, Xiaolei Song
    Abstract:

    Chemical exchange Saturation Transfer (CEST) has emerged as a novel MRI contrast mechanism that is well suited for molecular imaging studies. This new mechanism can be used to detect small amounts of contrast agent through the Saturation of rapidly exchanging protons on these agents, allowing a wide range of applications. CEST technology has a number of indispensable features, such as the possibility of simultaneous detection of multiple 'colors' of agents and of changes in their environment (e.g. pH, metabolites, etc.) through MR contrast. Currently, a large number of new imaging schemes and techniques are being developed to improve the temporal resolution and specificity and to correct for the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the last decade are summarized with the different imaging strategies and post-processing methods discussed from a practical point of view, including the description of their relative merits for the detection of CEST agents. The goal of the present work is to provide the reader with a fundamental understanding of the techniques developed, and to provide guidance to help refine future applications of this technology. This review is organized into three main sections ('Basics of CEST contrast', 'Implementation' and 'Post-processing'), and also includes a brief Introduction and Summary. The 'Basics of CEST contrast' section contains a description of the relevant background theory for Saturation Transfer and frequency-labeled Transfer, and a brief discussion of methods to determine exchange rates. The 'Implementation' section contains a description of the practical considerations in conducting CEST MRI studies, including the choice of magnetic field, pulse sequence, Saturation pulse, imaging scheme, and strategies to separate magnetization Transfer and CEST. The 'Post-processing' section contains a description of the typical image processing employed for B0 /B1 correction, Z-spectral interpolation, frequency-selective detection and improvement of CEST contrast maps.

  • in vivo multicolor molecular mr imaging using diamagnetic chemical exchange Saturation Transfer liposomes
    Magnetic Resonance in Medicine, 2012
    Co-Authors: Guanshu Liu, Matthew Moake, Yahel Harel, Christopher M Long, Kannie W Y Chan, Amanda Cardona, Muksit Jamil, Piotr Walczak, Assaf A Gilad
    Abstract:

    A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange Saturation Transfer MR contrast. This diamagnetic chemical exchange Saturation Transfer contrast is frequency-dependent, allowing the unique generation of “multicolor” images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange Saturation Transfer liposomes form an attractive novel platform for multicolor imaging in vivo. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

  • 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, Kannie W Y Chan, Yajie Liang, Amnon Barshir, 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 ...

Robert S. Balaban - One of the best experts on this subject based on the ideXlab platform.

  • a new class of contrast agents for mri based on proton chemical exchange dependent Saturation Transfer cest
    Journal of Magnetic Resonance, 2000
    Co-Authors: Kathleen M. Ward, Anthony H Aletras, Robert S. Balaban
    Abstract:

    Abstract It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using Saturation Transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent Saturation Transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via Saturation Transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5–7.6) and temperature (37°C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5,6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring –NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.

  • Determination of pH using water protons and chemical exchange dependent Saturation Transfer (CEST).
    Magnetic resonance in medicine, 2000
    Co-Authors: Kathleen M. Ward, Robert S. Balaban
    Abstract:

    Solution pH was measured using water proton NMR via chemical exchange dependent Saturation Transfer (CEST) with selected chemical exchange sites. Several useful pH-sensitive proton chemical exchange agents were found: 5,6-dihydrouracil, 5-hydroxytryptophan, and a combination of 5-hydroxytryptophan and 2-imidazolidinethione. A ratiometric approach was developed that permitted pH determinations that were independent of water T(1) or exchange site concentration.

  • A new class of contrast agents for MRI based on proton chemical exchange dependent Saturation Transfer (CEST).
    Journal of magnetic resonance (San Diego Calif. : 1997), 2000
    Co-Authors: Kathleen M. Ward, Anthony H Aletras, Robert S. Balaban
    Abstract:

    It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using Saturation Transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent Saturation Transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via Saturation Transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.