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Shelby Meier, Assaf A Gilad, J Anthony Brandon, Chenghao Qian, Erhe Gao, Jose F Abisambra, Moriel Vandsburger
Research into gene therapy for heart failure has gained renewed interest as a result of improved safety and availability of adeno-associated viral vectors (AAV). While magnetic resonance imaging (MRI) is standard for functional assessment of gene therapy outcomes, quantitation of gene transfer/expression relies upon tissue biopsy, fluorescence or nuclear imaging. Imaging of gene expression through the use of genetically encoded chemical exchange saturation transfer (CEST)-MRI reporter genes could be combined with clinical cardiac MRI methods to comprehensively probe therapeutic gene expression and subsequent outcomes...
March 15, 2018: Scientific Reports
Giuseppe Ferrauto, Enza Di Gregorio, Daniela Delli Castelli, Silvio Aime
PURPOSE: Magnetic resonance imaging has been used extensively to track in vivo implanted cells that have been previously labeled with relaxation enhancers. However, this approach is not suitable to track multiple cell populations, as it may lead to confounding results in case the contrast agent is released from the labeled cells. This paper demonstrates how the use of CEST agents can overcome these issues. After encapsulating paramagnetic lanthanide shift reagents, we may shift the absorption frequency of the intracellular water resonance (δIn ), thus generating frequency-encoding CEST responsive cells that can be visualized in the MR image by applying the proper RF irradiation...
March 7, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Cameron S Runte, Umang Jain, Landon J Getz, Sabrina Secord, Asaomi Kuwae, Akio Abe, Jason J LeBlanc, Andrew W Stadnyk, James B Kaper, Anne-Marie Hansen, Nikhil A Thomas
Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153, that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection...
March 6, 2018: Molecular Microbiology
Sangeeta Ray Banerjee, Xiaolei Song, Xing Yang, Il Minn, Ala Lisok, Yanrong Chen, Martin G Pomper, Peter C M van Zijl, Michael McMahon, Jian Chen
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an innovative molecular imaging technique in which contrast agents are labeled by saturating their exchangeable protons spins by radio frequency irradiation. Salicylic acid and its analogues are a promising class of highly sensitive, diamagnetic CEST agents. We synthesized polymeric agents grafted with salicylic acid moieties and a known high-affinity ligand targeting prostate-specific membrane antigen (PSMA) in a ~10:1 molar ratio to provide sufficient MRI sensitivity and receptor specificity...
March 5, 2018: Chemistry: a European Journal
Eleni Demetriou, Mohamed Tachrount, Moritz Zaiss, Karin Shmueli, Xavier Golay
PURPOSE: To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. METHODS: A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition...
March 5, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Gigin Lin, Chyong-Huey Lai, Tzu-Chen Yen
Molecular imaging (mainly PET and MR imaging) has played important roles in gynecologic oncology. Emerging MR-based technologies, including DWI, CEST, DCE-MR imaging, MRS, and DNP, as well as FDG-PET and many novel PET radiotracers, will continuously improve practices. In combination with radiomics analysis, a new era of decision making in personalized medicine and precisely guided radiation treatment planning or real-time surgical interventions is being entered into, which will directly impact on patient survival...
April 2018: PET Clinics
Kyle M Jones, Carol A Stuehm, Charles C Hsu, Phillip H Kuo, Mark D Pagel, Edward A Randtke
Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-millisecond saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.03-ppm intervals. The Fourier transform of each image was used to calculate the difference in phase angle between adjacent pixels in the longitudinal direction of the respiratory motion...
December 2017: Tomography: a Journal for Imaging Research
N A da Silva, P Lohmann, J Fairney, A W Magill, A-M Oros Peusquens, C-H Choi, R Stirnberg, G Stoffels, N Galldiks, X Golay, K-J Langen, N Jon Shah
PURPOSE: PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2-18 F-fluoroethyl)-L-tyrosine (18 F-FET). METHODS: Eight patients with gliomas were investigated simultaneously with18 F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner...
February 24, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Daniel F Gochberg, Mark D Does, Zhongliang Zu, Christopher L Lankford
Chemical exchange saturation transfer (CEST) is an imaging method based on magnetization exchange between solutes and water. This exchange generates changes in the measured signal after off-resonance radiofrequency irradiation. Although the analytic solution for CEST with continuous wave (CW) irradiation has been determined, most studies are performed using pulsed irradiation. In this work, we derive an analytic solution for the CEST signal after pulsed irradiation that includes both short-time rotation effects and long-time saturation effects in a two-pool system corresponding to water and a low-concentration exchanging solute pool...
February 20, 2018: NMR in Biomedicine
Janin Lautenschläger, Amberley D Stephens, Giuliana Fusco, Florian Ströhl, Nathan Curry, Maria Zacharopoulou, Claire H Michel, Romain Laine, Nadezhda Nespovitaya, Marcus Fantham, Dorothea Pinotsi, Wagner Zago, Paul Fraser, Anurag Tandon, Peter St George-Hyslop, Eric Rees, Jonathan J Phillips, Alfonso De Simone, Clemens F Kaminski, Gabriele S Kaminski Schierle
Alpha-synuclein is known to bind to small unilamellar vesicles (SUVs) via its N terminus, which forms an amphipathic alpha-helix upon membrane interaction. Here we show that calcium binds to the C terminus of alpha-synuclein, therewith increasing its lipid-binding capacity. Using CEST-NMR, we reveal that alpha-synuclein interacts with isolated synaptic vesicles with two regions, the N terminus, already known from studies on SUVs, and additionally via its C terminus, which is regulated by the binding of calcium...
February 19, 2018: Nature Communications
Samira M Abozeid, Eric M Snyder, Timothy Y Tittiris, Charles M Steuerwald, Alexander Y Nazarenko, Janet R Morrow
High-spin Co(II) complexes are promising for development as paraCEST agents (paraCEST = paramagnetic chemical exchange saturation transfer) for magnetic resonance imaging applications. The first examples of Co(II) paraCEST agents with bound water ligands are presented here. Four Co(II) macrocyclic complexes based on 1,4,7-triazacyclononane and containing either pendent alcohol or pendent amide groups were prepared. Two of the macrocycles encapsulate the Co(II) and contain no water ligands as shown by X-ray crystallographic studies, and two complexes have macrocycles with only five ligand donor groups to leave an open coordination site for bound water...
February 7, 2018: Inorganic Chemistry
Daniela Delli Castelli, Lorenzo Tei, Fabio Carniato, Silvio Aime, Mauro Botta
An unexpectedly slow exchange rate has been observed for the coordinated water molecule of [Yb(AAZTA)(H2O)]- using 1H-NMR and CEST-MRI studies. This made it possible for the first time to exploit the bound water molecule of a LnIII complex with carboxylic donor groups for CEST imaging. This result envisages the development of a new family of thermodynamically stable ParaCEST probes based on anionic chelates.
February 7, 2018: Chemical Communications: Chem Comm
Lin Chen, Xiang Xu, Haifeng Zeng, Kannie W Y Chan, Nirbhay Yadav, Shuhui Cai, Kathryn J Schunke, Nauder Faraday, Peter C M van Zijl, Jiadi Xu
PURPOSE: To develop a method that can separate and quantify the fast (>1 kHz) and slow exchange transfer and magnetization transfer components in Z-spectra. METHODS: Z-spectra were recorded as a function of mixing time using a train of selective pulses providing variable-delay multipulse build-up curves. Fast and slow transfer components in the Z-spectra were separated and quantified on a voxel-by-voxel basis by fitting the mixing time-dependent CEST signal using a 3-pool model...
February 5, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Ulrich Flögel, Anke Schlüter, Christoph Jacoby, Sebastian Temme, J Paul Banga, Anja Eckstein, Jürgen Schrader, Utta Berchner-Pfannschmidt
PURPOSE: To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling. METHODS: To this end, we utilized a murine model of GO induced by immunization with a human thyroid-stimulating hormone receptor A-subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl) immunized with β-galactasidose plasmid. From these, 17 GO and 12 Ctrl mice were subjected to multimodal MRI at 9...
January 27, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Moritz Zaiss, Philipp Ehses, Klaus Scheffler
Gradient echo (GRE)-based acquisition provides a robust readout method for chemical exchange saturation transfer (CEST) at ultrahigh field (UHF). To develop a snapshot-CEST approach, the transient GRE signal and point spread function were investigated in detail, leading to optimized measurement parameters and reordering schemes for fast and robust volumetric CEST imaging. Simulation of the transient GRE signal was used to determine the optimal sequence parameters and the maximum feasible number of k-space lines...
January 26, 2018: NMR in Biomedicine
Valérie C Pierre, Sarah M Harris, Sylvie L Pailloux
Magnetic resonance imaging (MRI) has emerged over the years as one of the preferred modalities for medical diagnostic and biomedical research. It has the advantage over other imaging modalities such as positron emission tomography and X-ray of affording high resolution three-dimensional images of the body without using harmful radiation. The use of contrast agents has further expanded this technique by increasing the contrast between regions where they accumulate and background tissues. As MRI most often measures the relaxation rate of water throughout the body, contrast agents function by modulating the intensity of the water signal either via improved relaxation or via saturation transfer to selected exchangeable proton...
January 22, 2018: Accounts of Chemical Research
Tairan Yuwen, Lewis E Kay
Chemical exchange saturation transfer (CEST) experiments are becoming increasingly popular for investigating biomolecular exchange dynamics with rates on the order of approximately 50-500 s-1 and a rich toolkit of different methods has emerged over the past few years. Typically, experiments are based on the evolution of longitudinal magnetization, or in some cases two-spin order, during a fixed CEST relaxation delay, with the same class of magnetization prepared at the start and selected at end of the CEST period...
January 19, 2018: Journal of Biomolecular NMR
Pedro Ramos-Cabrer, Daniel Padro
Stroke consists of the loss of cerebral functions resulting from the interruption of blood supply to a region of the brain, and represents the second cause of death and the leading cause of major disability in adults in Europe. Stroke is a very active field of research at preclinical and clinical levels, and Magnetic Resonance Imaging (MRI) is one of the most powerful tools that scientist and clinicians have for the study of the onset, evolution and consequences of this devastating disease, as well as for the monitoring of the success of available treatments, or for the development of novel therapeutic strategies...
2018: Methods in Molecular Biology
N Lokesh, Andreas Seegerer, Johnny Hioe, Ruth M Gschwind
The low sensitivity of NMR and transient key intermediates below detection limit are the central problems studying reaction mechanisms by NMR. Sensitivity can be enhanced by hyperpolarization techniques such as dynamic nuclear polarization or the incorporation/interaction of special hyperpolarized molecules. However, all of these techniques require special equipment, are restricted to selective reactions or undesirably influence the reaction pathways. Here, we apply the Chemical Exchange Saturation Transfer (CEST) technique for the first time to NMR detect and characterize previously unobserved transient reaction intermediates in organocatalysis...
January 16, 2018: Journal of the American Chemical Society
Tsang-Wei Tu, Wael G Ibrahim, Neekita Jikaria, Jeeva P Munasinghe, Jaclyn A Witko, Dima A Hammoud, Joseph A Frank
Metabolic abnormalities are commonly observed in traumatic brain injury (TBI) patients exhibiting long-term neurological deficits. This study investigated the feasibility and reproducibility of using chemical exchange saturation transfer (CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the selective saturation for enhancing the endogenous contrast-weighting of the proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in the resting rat brain...
January 12, 2018: Scientific Reports
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