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Michael T McMahon, Assaf A Gilad
Chemical exchange saturation transfer (CEST) is a powerful new tool well suited for molecular imaging. This technology enables the detection of low concentration probes through selective labeling of rapidly exchanging protons or other spins on the probes. In this review, we will highlight the unique features of CEST imaging technology and describe the different types of CEST agents that are suited for molecular imaging studies, including CEST theranostic agents, CEST reporter genes, and CEST environmental sensors...
October 2016: Topics in Magnetic Resonance Imaging: TMRI
Robert J Harris, Timothy F Cloughesy, Linda M Liau, Phioanh L Nghiemphu, Albert Lai, Whitney B Pope, Benjamin M Ellingson
Acidity within the extracellular milieu is a hallmark of cancer. There is a current need for fast, high spatial resolution pH imaging techniques for clinical evaluation of cancers, including gliomas. Chemical exchange saturation transfer (CEST) MRI targeting fast-exchanging amine protons can be used to obtain high-resolution pH-weighted images, but conventional CEST acquisition strategies are slow. There is also a need for more accurate MR simulations to better understand the effects of amine CEST pulse sequence parameters on pH-weighted image contrast...
September 15, 2016: NMR in Biomedicine
Gen Yan, Tao Zhang, Zhuozhi Dai, Meizhi Yi, Yanlong Jia, Tingting Nie, Handi Zhang, Gang Xiao, Renhua Wu
PURPOSE: We developed a novel magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer (CEST) for GABA imaging and investigated the concentration-dependent CEST effect ofGABA in a rat model of brain tumor with blood-brain barrier (BBB) disruption. MATERIALS AND METHODS: All MRI studies were performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at 7.0 T, 37°C, and a pH of 7.0 using varying B1 amplitudes. CEST images of phantoms with different concentrations of GABA solutions (pH, 7...
2016: PloS One
Iris Yuwen Zhou, Taylor L Fuss, Takahiro Igarashi, Weiping Jiang, Xin Zhou, Leo L Cheng, Phillip Zhe Sun
Chemical exchange saturation transfer (CEST) provides sensitive 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...
October 6, 2016: Analytical Chemistry
Kimberly L Desmond, Hatef Mehrabian, Sofia Chavez, Arjun Sahgal, Hany Soliman, Radoslaw Rola, Greg J Stanisz
PURPOSE: The purpose of this work was to determine the predictive value of chemical exchange saturation transfer (CEST) metrics in brain metastases treated with stereotactic radiosurgery (SRS). METHODS: CEST spectra at a radiofrequency power of 0.52 µT were collected on a 3 Tesla (T) magnetic resonance imaging from 25 patients at three time points: pretreatment, 1 week, and 1 month post-treatment. Amide proton transfer-weighted images and maps of the amplitude and width of Lorentzian-shaped CEST peaks and the relaxation-compensated AREX metric were constructed at the offset frequencies of amide, amine, and relayed nuclear Overhauser effect (NOE) from aliphatic groups as well as the broad magnetization transfer effect...
September 30, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Kevin J Ray, James R Larkin, Yee K Tee, Alexandre A Khrapitchev, Gogulan Karunanithy, Michael Barber, Andrew J Baldwin, Michael A Chappell, Nicola R Sibson
The purpose of this study was to develop realistic phantom models of the intracellular environment of metastatic breast tumour and naïve brain, and using these models determine an analysis metric for quantification of CEST MRI data that is sensitive to only labile proton exchange rate and concentration. The ability of the optimal metric to quantify pH differences in the phantoms was also evaluated. Novel phantom models were produced, by adding perchloric acid extracts of either metastatic mouse breast carcinoma cells or healthy mouse brain to bovine serum albumin...
September 30, 2016: NMR in Biomedicine
Binhan Yu, Daiwen Yang
Proteins are dynamic over a wide range of timescales, but determining the number of distinct dynamic processes and identifying functionally relevant dynamics are still challenging. Here we present the study on human intestinal fatty acid binding protein (hIFABP) using a novel analysis of (15)N relaxation dispersion (RD) and chemical shift saturation transfer (CEST) experiments. Through combined analysis of the two types of experiments, we found that hIFABP exists in a four-state equilibrium in which three minor states interconvert directly with the major state...
September 28, 2016: Scientific Reports
J Klein, G Czarnota, W Lam, C Tarapacki, G Stanisz
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Zhengwei Zhou, Maxim Bez, Wafa Tawackoli, Joseph Giaconi, Dmitriy Sheyn, Sandra de Mel, Marcel M Maya, Barry D Pressman, Zulma Gazit, Gadi Pelled, Dan Gazit, Debiao Li
PURPOSE: Previous studies have associated low pH in intervertebral discs (IVDs) with discogenic back pain. The purpose of this study was to determine whether quantitative CEST (qCEST) MRI can be used to detect pH changes in IVDs in vivo. METHODS: The exchange rate ksw between glycosaminoglycan (GAG) protons and water protons was determined from qCEST analysis. Its dependence on pH value was investigated in GAG phantoms with varying pH and concentrations. The relationship between ksw and pH was studied further in vivo in a porcine model on a 3T MR scanner and validated using a pH meter...
September 26, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Vitaliy Khlebnikov, Jeroen C W Siero, Jannie Wijnen, Fredy Visser, Peter R Luijten, Dennis W J Klomp, Hans Hoogduin
Measurement of Chemical Exchange Saturation Transfer (CEST) is providing tissue physiology dependent contrast, e.g. by looking at Amide and NOE (Nuclear Overhauser Enhancement) effects. CEST is unique in providing quantitative metabolite information at high imaging resolution. However, direct comparison of Amide and NOE effects between different tissues may result in wrong conclusions on the metabolite concentration due to the additional contributors to the observed CEST contrast, such as water content (WC) and water T1 relaxation (T1w)...
September 16, 2016: Journal of Magnetic Resonance
Dario L Longo, Antonietta Bartoli, Lorena Consolino, Paola Bardini, Francesca Arena, Markus Schwaiger, Silvio Aime
The vast majority of cancers exhibit increased glucose uptake and glycolysis regardless of oxygen availability. This metabolic shift leads to an enhanced production of lactic acid that decreases extracellular pH (pHe), a hallmark of the tumour microenvironment. In this way, dysregulated tumour pHe and up-regulated glucose metabolism are linked tightly and their relative assessment may be useful to gain understanding of the underlying biology. Here we investigated non-invasively the in vivo correlation between tumour (18)F-FDG uptake and extracellular pH values in a murine model of HER2+ breast cancer...
September 20, 2016: Cancer Research
Yanfei Wang, Ivan J Dmochowski
Molecular imaging holds considerable promise for elucidating biological processes in normal physiology as well as disease states, by determining the location and relative concentration of specific molecules of interest. Proton-based magnetic resonance imaging ((1)H MRI) is nonionizing and provides good spatial resolution for clinical imaging but lacks sensitivity for imaging low-abundance (i.e., submicromolar) molecular markers of disease or environments with low proton densities. To address these limitations, hyperpolarized (hp) (129)Xe NMR spectroscopy and MRI have emerged as attractive complementary methodologies...
October 18, 2016: Accounts of Chemical Research
Kamini Marathe, Nevin McVicar, Alex Li, Miranda Bellyou, Susan Meakin, Robert Bartha
Reversal of the intracellular/extracellular pH gradient is a hallmark of malignant tumors and is an important consideration in evaluating tumor growth potential and the effectiveness of anticancer therapies. Glioblastoma multiforme (GBM) brain tumors have increased expression of the carbonic anhydrase (CA) isozymes CAII, CAIX and CAXII that contribute to the altered regulation of intracellular pH (pHi). The anti-epileptic drug topiramate (TPM) inhibits CA action and may acidify the tumor intracellular compartment...
September 9, 2016: Journal of Neuro-oncology
Michal Rivlin, Gil Navon
The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results...
2016: Scientific Reports
Annasofia Anemone, Lorena Consolino, Dario Livio Longo
OBJECTIVES: X-ray iodinated contrast media have been shown to generate contrast in MR images when used with the chemical exchange saturation transfer (CEST) approach. The aim of this study is to compare contrast enhancement (CE) capabilities and perfusion estimates between radiographic molecules and a Gd-based contrast agent in two tumour murine models with different vascularization patterns. METHODS: MRI-CEST and MRI-CE T1w images were acquired in murine TS/A and 4 T1 breast tumours upon sequential i...
August 29, 2016: European Radiology
B Wu, G Warnock, M Zaiss, C Lin, M Chen, Z Zhou, L Mu, D Nanz, R Tuura, G Delso
The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules...
December 2016: EJNMMI Physics
Haifeng Zeng, Jiadi Xu, Nirbhay N Yadav, Michael T McMahon, Bradley Harden, Dominique Frueh, Peter C M van Zijl
A two-step heteronuclear enhancement approach was combined with chemical exchange saturation transfer (CEST) to magnify (15)N MRI signal of molecules through indirect detection via water protons. Previous CEST studies have been limited to radiofrequency (rf) saturation transfer or excitation transfer employing protons. Here, the signal of (15)N is detected indirectly through the water signal by first inverting selectively protons that are scalar-coupled to (15)N in the urea molecule, followed by chemical exchange of the amide proton to bulk water...
September 7, 2016: Journal of the American Chemical Society
Kejia Cai, Rong-Wen Tain, Xiaohong Joe Zhou, Frederick C Damen, Alessandro M Scotti, Hari Hariharan, Harish Poptani, Ravinder Reddy
PURPOSE: Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression...
August 19, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Rongwen Tain, He N Xu, Xiaohong J Zhou, Lin Z Li, Kejia Cai
Developing imaging biomarkers for non-invasive measurement of the tissue redox state is a key research area. Recently, we presented the first non-invasive MR imaging method that demonstrated the correlation between the endogenous chemical exchange saturation transfer (CEST) contrast and the tissue redox state. It is well known that the broadband magnetization transfer (MT) can occur via chemical exchange (CEST) and/or dipole-dipole interactions. The present study investigated if the broadband MT also correlated with the tissue redox state...
2016: Advances in Experimental Medicine and Biology
Anja Müller-Lutz, Tom Cronenberg, Christoph Schleich, Frithjof Wickrath, Moritz Zaiss, Johannes Boos, Hans-Jörg Wittsack
PURPOSE: To investigate, if a train of spin-lock pulses (chemical exchange saturation transfer with spin-lock pulses = CESL) improves biochemical glycosaminoglycan imaging compared with conventional chemical exchange saturation transfer with Gaussian-shaped pulses (CEST) in lumbar intervertebral discs. METHODS: T2 , CEST, and CESL imaging was performed in lumbar intervertebral discs of 15 healthy volunteers at 3 Tesla. Mean and standard deviation of the asymmetric magnetization transfer ratio (MTRasym ), the asymmetric spin-lock ratio (SLRasym ) and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF)...
August 3, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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