Clinical applications of chemical exchange saturation transfer (CEST) MRI

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has been developed and employed in multiple clinical imaging research centers worldwide. Selective radiofrequency (RF) saturation pulses with standard 2D and 3D MRI acquisition schemes are now routinely performed, and CEST MRI can produce semiquantitative results using magnetization transfer ratio asymmetry (MTRasym) analysis while accounting for B0 inhomogeneity. Faster clinical CEST MRI acquisition methods and more quantitative acquisition and analysis routines are under development. Endogenous biomolecules with amide, amine, and hydroxyl groups have been detected during clinical CEST MRI studies, and exogenous CEST agents have also been administered to patients. These CEST MRI tools show promise for contributing to assessments of cerebral ischemia, neurological disorders, lymphedema, osteoarthritis, muscle physiology, and solid tumors. This review summarizes the salient features of clinical CEST MRI protocols and critically evaluates the utility of CEST MRI for these clinical imaging applications.

[1]  Gil Navon,et al.  Molecular imaging of tumors and metastases using chemical exchange saturation transfer (CEST) MRI , 2013, Scientific Reports.

[2]  A. Müller-Lutz,et al.  Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results , 2015, Skeletal Radiology.

[3]  B Wu,et al.  An overview of CEST MRI for non-MR physicists , 2016, EJNMMI Physics.

[4]  Jiadi Xu,et al.  Variable delay multi‐pulse train for fast chemical exchange saturation transfer and relayed‐nuclear overhauser enhancement MRI , 2014, Magnetic resonance in medicine.

[5]  Gil Navon,et al.  Functional molecular imaging of tumors by chemical exchange saturation transfer MRI of 3‐O‐Methyl‐D‐glucose , 2014, Magnetic resonance in medicine.

[6]  Erik Tryggestad,et al.  Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides , 2010, Nature Medicine.

[7]  Robert D. Stevens,et al.  Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients , 2015, Tomography.

[8]  H. Kauczor,et al.  Comparison of biochemical cartilage imaging techniques at 3 T MRI. , 2014, Osteoarthritis and cartilage.

[9]  Peter Bachert,et al.  A combined analytical solution for chemical exchange saturation transfer and semi‐solid magnetization transfer , 2015, NMR in biomedicine.

[10]  M. Chappell,et al.  Quantification of amide proton transfer effect pre‐ and post‐gadolinium contrast agent administration , 2014, Journal of magnetic resonance imaging : JMRI.

[11]  Robert E Lenkinski,et al.  On-resonance low B1 pulses for imaging of the effects of PARACEST agents. , 2005, Journal of magnetic resonance.

[12]  Richard A. E. Edden,et al.  Nuclear Overhauser enhancement (NOE) imaging in the human brain at 7T , 2013, NeuroImage.

[13]  Enzo Terreno,et al.  Iopamidol as a responsive MRI‐chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T , 2011, Magnetic resonance in medicine.

[14]  M. Pagel,et al.  Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent. , 2016, Chemistry.

[15]  Edward A. Randtke,et al.  A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. , 2016, Contrast media & molecular imaging.

[16]  Vipul R Sheth,et al.  Measuring in vivo tumor pHe with CEST‐FISP MRI , 2012, Magnetic resonance in medicine.

[17]  Edward A. Randtke,et al.  QUESPOWR MRI: QUantification of Exchange as a function of Saturation Power On the Water Resonance. , 2016, Journal of magnetic resonance.

[18]  Mark D Pagel,et al.  An overview of responsive MRI contrast agents for molecular imaging. , 2008, Frontiers in bioscience : a journal and virtual library.

[19]  Peter Bachert,et al.  Inverse Z‐spectrum analysis for spillover‐, MT‐, and T1‐corrected steady‐state pulsed CEST‐MRI – application to pH‐weighted MRI of acute stroke , 2014, NMR in biomedicine.

[20]  Young Han Lee,et al.  Assessment of the patellofemoral cartilage: Correlation of knee pain score with magnetic resonance cartilage grading and magnetization transfer ratio asymmetry of glycosaminoglycan chemical exchange saturation transfer. , 2017, Magnetic resonance imaging.

[21]  Ravinder Reddy,et al.  Imaging of glutamate in the spinal cord using GluCEST , 2013, NeuroImage.

[22]  H. Schlemmer,et al.  A new contrast in MR mammography by means of chemical exchange saturation transfer (CEST) imaging at 3 Tesla: preliminary results. , 2011, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.

[23]  Edward A. Randtke,et al.  A catalyCEST MRI contrast agent that detects the enzyme-catalyzed creation of a covalent bond. , 2013, Journal of the American Chemical Society.

[24]  Yin Wu,et al.  Investigation of the performance of variable-density Z-spectrum acquisition scheme in MR chemical exchange saturation transfer effect quantification , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[25]  Ravinder Reddy,et al.  Method for high‐resolution imaging of creatine in vivo using chemical exchange saturation transfer , 2014, Magnetic resonance in medicine.

[26]  Ravinder Reddy,et al.  High quality three‐dimensional gagCEST imaging of in vivo human knee cartilage at 7 Tesla , 2017, Magnetic resonance in medicine.

[27]  O. Togao,et al.  Glycosaminoglycan chemical exchange saturation transfer in human lumbar intervertebral discs: Effect of saturation pulse and relationship with low back pain , 2017, Journal of magnetic resonance imaging : JMRI.

[28]  Jinyuan Zhou,et al.  Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer , 2016, Scientific Reports.

[29]  Hairong Zheng,et al.  A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging. , 2015, Contrast media & molecular imaging.

[30]  R E Lenkinski,et al.  Keyhole chemical exchange saturation transfer , 2012, Magnetic resonance in medicine.

[31]  Ravinder Reddy,et al.  Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T , 2012, Magnetic resonance in medicine.

[32]  Enzo Terreno,et al.  CMR2009: 11.02: Evaluating iopamidol as pH-responsive CEST agent at 3 and 7 T , 2009 .

[33]  Tao Jin,et al.  Spin‐locking versus chemical exchange saturation transfer MRI for investigating chemical exchange process between water and labile metabolite protons , 2011, Magnetic resonance in medicine.

[34]  Xuna Zhao,et al.  Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T , 2011, Magnetic resonance in medicine.

[35]  Jinyuan Zhou,et al.  Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments , 2004, Magnetic resonance in medicine.

[36]  Comparison of divalent transition metal ion paraCEST MRI contrast agents , 2014, JBIC Journal of Biological Inorganic Chemistry.

[37]  Phillip Zhe Sun,et al.  Association between pH-Weighted Endogenous Amide Proton Chemical Exchange Saturation Transfer MRI and Tissue Lactic Acidosis during Acute Ischemic Stroke , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[38]  Yi Zhang,et al.  Simultaneous detection and separation of hyperacute intracerebral hemorrhage and cerebral ischemia using amide proton transfer MRI , 2015, Magnetic resonance in medicine.

[39]  Koji Yamashita,et al.  Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. , 2014, Neuro-oncology.

[40]  Kyle M. Jones,et al.  A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH. , 2015, Contrast media & molecular imaging.

[41]  A. Müller-Lutz,et al.  Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs. , 2016, Magnetic resonance imaging.

[42]  Benjamin M Ellingson,et al.  Simulation, phantom validation, and clinical evaluation of fast pH‐weighted molecular imaging using amine chemical exchange saturation transfer echo planar imaging (CEST‐EPI) in glioma at 3 T , 2016, NMR in biomedicine.

[43]  Jinyuan Zhou,et al.  Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging , 2008, Magnetic resonance in medicine.

[44]  Vipul R Sheth,et al.  Improved pH measurements with a single PARACEST MRI contrast agent. , 2012, Contrast media & molecular imaging.

[45]  Kyle M. Jones,et al.  Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI , 2017, Magnetic resonance in medicine.

[46]  Daniel Paech,et al.  Downfield‐NOE‐suppressed amide‐CEST‐MRI at 7 Tesla provides a unique contrast in human glioblastoma , 2017, Magnetic resonance in medicine.

[47]  A. O. Scott,et al.  Assessment of lymphatic impairment and interstitial protein accumulation in patients with breast cancer treatment‐related lymphedema using CEST MRI , 2016, Magnetic resonance in medicine.

[48]  M. Pagel,et al.  Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI , 2014, Magnetic resonance in medicine.

[49]  Q. Chan,et al.  Assessment of glycosaminoglycan distribution in human lumbar intervertebral discs using chemical exchange saturation transfer at 3 T: feasibility and initial experience , 2011, NMR in biomedicine.

[50]  Peter Jezzard,et al.  Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging , 2014, Brain : a journal of neurology.

[51]  E. Kanal,et al.  Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. , 2007, Radiology.

[52]  P. Barker,et al.  The role of amide proton transfer imaging in detecting active malignant glioma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  Bram Stieltjes,et al.  7 tesla imaging of cerebral radiation necrosis after arteriovenous malformations treatment using amide proton transfer (APT) imaging , 2012, Journal of magnetic resonance imaging : JMRI.

[54]  Seth A. Smith,et al.  Added value of amide proton transfer imaging to conventional and perfusion MR imaging for evaluating the treatment response of newly diagnosed glioblastoma , 2016, European Radiology.

[55]  Craig K. Jones,et al.  Four‐pool modeling of proton exchange processes in biological systems in the presence of MRI–paramagnetic chemical exchange saturation transfer (PARACEST) agents , 2008, Magnetic resonance in medicine.

[56]  Daniel Paech,et al.  Correction of B1‐inhomogeneities for relaxation‐compensated CEST imaging at 7 T , 2015, NMR in biomedicine.

[57]  Nirbhay N. Yadav,et al.  Tuning phenols with Intra-Molecular bond Shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents. , 2014, Chemistry.

[58]  R. Lenkinski,et al.  UCEPR: Ultrafast localized CEST‐spectroscopy with PRESS in phantoms and in vivo , 2016, Magnetic resonance in medicine.

[59]  Thomas Benner,et al.  Fast multislice pH‐weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation , 2011, Magnetic resonance in medicine.

[60]  V. Jellús,et al.  Pilot study of Iopamidol-based quantitative pH imaging on a clinical 3T MR scanner , 2014, Magnetic Resonance Materials in Physics, Biology and Medicine.

[61]  R M Henkelman,et al.  Modeling magnetization transfer for biological-like systems using a semi-solid pool with a super-Lorentzian lineshape and dipolar reservoir. , 1995, Journal of magnetic resonance. Series B.

[62]  Ravinder Reddy,et al.  Mapping glutamate in subcortical brain structures using high‐resolution GluCEST MRI , 2013, NMR in biomedicine.

[63]  Bennett A Landman,et al.  Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments , 2009, Magnetic resonance in medicine.

[64]  J A Frank,et al.  Perfusion imaging with compensation for asymmetric magnetization transfer effects , 1996, Magnetic resonance in medicine.

[65]  B. Hills,et al.  Proton NMR relaxation studies of aqueous polysaccharide systems , 1991 .

[66]  Ravinder Reddy,et al.  In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T , 2014, Journal of magnetic resonance imaging : JMRI.

[67]  Brian Litt,et al.  Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy , 2015, Science Translational Medicine.

[68]  Mark D Pagel,et al.  A review of responsive MRI contrast agents: 2005-2014. , 2015, Contrast media & molecular imaging.

[69]  Matthew E Merritt,et al.  Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI , 2005, Magnetic resonance in medicine.

[70]  Jinyuan Zhou,et al.  MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast , 2010, NeuroImage.

[71]  Peter Bachert,et al.  Cartilage quality assessment by using glycosaminoglycan chemical exchange saturation transfer and (23)Na MR imaging at 7 T. , 2011, Radiology.

[72]  Peter Bachert,et al.  Relaxation‐compensated CEST‐MRI at 7 T for mapping of creatine content and pH – preliminary application in human muscle tissue in vivo , 2015, NMR in biomedicine.

[73]  Nirbhay N. Yadav,et al.  Imaging of Endogenous Exchangeable Proton Signals in the Human Brain Using Frequency Labeled Exchange Transfer Imaging , 2013, Magnetic resonance in medicine.

[74]  Ravinder Reddy,et al.  On B1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T , 2013, Magnetic resonance in medicine.

[75]  Hye-Young Heo,et al.  Applying amide proton transfer‐weighted MRI to distinguish pseudoprogression from true progression in malignant gliomas , 2016, Journal of magnetic resonance imaging : JMRI.

[76]  P. Jezzard,et al.  Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients , 2014, NMR in biomedicine.

[77]  Yoshinori Kato,et al.  Natural D‐glucose as a biodegradable MRI contrast agent for detecting cancer , 2012, Magnetic resonance in medicine.

[78]  Kai Zhang,et al.  Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis , 2015, Molecular Imaging and Biology.

[79]  Jinyuan Zhou,et al.  Optimization of the irradiation power in chemical exchange dependent saturation transfer experiments. , 2005, Journal of magnetic resonance.

[80]  M. McMahon,et al.  Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. , 2015, Contrast media & molecular imaging.

[81]  Jiadi Xu,et al.  Magnetization transfer contrast–suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T , 2016, Magnetic resonance in medicine.

[82]  Vaibhav A. Janve,et al.  A new method for detecting exchanging amide protons using chemical exchange rotation transfer , 2013, Magnetic resonance in medicine.

[83]  A. Müller-Lutz,et al.  Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Healthy Volunteers , 2016, Spine.

[84]  Jiadi Xu,et al.  On‐resonance variable delay multipulse scheme for imaging of fast‐exchanging protons and semisolid macromolecules , 2017, Magnetic resonance in medicine.

[85]  Peter Bachert,et al.  Aggregation‐induced changes in the chemical exchange saturation transfer (CEST) signals of proteins , 2017, NMR in biomedicine.

[86]  R S Balaban,et al.  A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). , 2000, Journal of magnetic resonance.

[87]  Mary E. Spilker,et al.  A Review of Imaging Agent Development , 2009, The AAPS Journal.

[88]  J. Gerss,et al.  Facet tropism and facet joint orientation: risk factors for the development of early biochemical alterations of lumbar intervertebral discs. , 2016, Osteoarthritis and cartilage.

[89]  R. Vandenberghe,et al.  Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807 , 2016, Molecular imaging.

[90]  R V Mulkern,et al.  The general solution to the Bloch equation with constant rf and relaxation terms: application to saturation and slice selection. , 1993, Medical physics.

[91]  Kyle M. Jones,et al.  Evaluations of Tumor Acidosis Within In Vivo Tumor Models Using Parametric Maps Generated with AcidoCEST MRI , 2015, Molecular Imaging and Biology.

[92]  Nirbhay N. Yadav,et al.  Chemical exchange saturation transfer (CEST): What is in a name and what isn't? , 2011, Magnetic resonance in medicine.

[93]  Gil Navon,et al.  Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST) , 2008, Proceedings of the National Academy of Sciences.

[94]  Jinyuan Zhou,et al.  A Simple Model for Understanding the Origin of the Amide Proton Transfer MRI Signal in Tissue , 2012, Applied magnetic resonance.

[95]  T. Tartaglione,et al.  Iomeprol versus iopamidol in contrast-enhanced computed tomography of thoracic and abdominal organs. , 1994, European Journal of Radiology.

[96]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[97]  Jinyuan Zhou,et al.  Quantitative description of the asymmetry in magnetization transfer effects around the water resonance in the human brain , 2007, Magnetic resonance in medicine.

[98]  A. Müller-Lutz,et al.  Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis , 2015, Journal of magnetic resonance imaging : JMRI.

[99]  David C. Alsop,et al.  Contributors to contrast between glioma and brain tissue in chemical exchange saturation transfer sensitive imaging at 3Tesla , 2014, NeuroImage.

[100]  Gil Navon,et al.  Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors , 2016, Scientific Reports.

[101]  V. Mlynárik,et al.  Reproducibility and regional variations of an improved gagCEST protocol for the in vivo evaluation of knee cartilage at 7 T , 2016, Magnetic Resonance Materials in Physics, Biology and Medicine.

[102]  O. Warburg On the origin of cancer cells. , 1956, Science.

[103]  Alexej Jerschow,et al.  Ultrafast scanning of exchangeable sites by NMR spectroscopy. , 2013, Angewandte Chemie.

[104]  Thomas E. Yankeelov,et al.  Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and Interpretation , 2012, Pharmaceutics.

[105]  A. Sorensen,et al.  Simulation and optimization of pulsed radio frequency irradiation scheme for chemical exchange saturation transfer (CEST) MRI—demonstration of pH‐weighted pulsed‐amide proton CEST MRI in an animal model of acute cerebral ischemia , 2011, Magnetic resonance in medicine.

[106]  M. McMahon,et al.  Developing imidazoles as CEST MRI pH sensors. , 2016, Contrast media & molecular imaging.

[107]  Debiao Li,et al.  pH-weighted molecular imaging of gliomas using amine chemical exchange saturation transfer MRI. , 2015, Neuro-oncology.

[108]  Jinyuan Zhou,et al.  Chemical exchange saturation transfer imaging and spectroscopy , 2006 .

[109]  A Gregory Sorensen,et al.  Correction for artifacts induced by B0 and B1 field inhomogeneities in pH‐sensitive chemical exchange saturation transfer (CEST) imaging , 2007, Magnetic resonance in medicine.

[110]  Hye-Young Heo,et al.  Whole‐brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low‐power steady‐state pulsed chemical exchange saturation transfer (CEST) imaging at 7T , 2016, Journal of magnetic resonance imaging : JMRI.

[111]  Erin K. Englund,et al.  Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle , 2017, NMR in biomedicine.

[112]  Mark A Griswold,et al.  PARACEST MRI with improved temporal resolution , 2009, Magnetic resonance in medicine.

[113]  E. Oldfield,et al.  Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI. , 2016, Chemistry.

[114]  Martin G Pomper,et al.  Salicylic acid and analogues as diaCEST MRI contrast agents with highly shifted exchangeable proton frequencies. , 2013, Angewandte Chemie.

[115]  John A. Detre,et al.  Magnetic Resonance Imaging of Glutamate , 2011, Nature Medicine.

[116]  Xavier Golay,et al.  Amide proton transfer imaging of human brain tumors at 3T , 2006, Magnetic resonance in medicine.

[117]  A. Baker,et al.  Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI , 2016, Molecular imaging.

[118]  R. Wu,et al.  Magnetization Transfer Prepared Gradient Echo MRI for CEST Imaging , 2014, PloS one.

[119]  O. Togao,et al.  Effect of the saturation pulse duration on chemical exchange saturation transfer in amide proton transfer MR imaging: a phantom study , 2015, Radiological Physics and Technology.

[120]  R. Bartha,et al.  Topiramate induces acute intracellular acidification in glioblastoma , 2016, Journal of Neuro-Oncology.

[121]  Benjamin Schmitt,et al.  Relaxation-compensated CEST-MRI of the human brain at 7T: Unbiased insight into NOE and amide signal changes in human glioblastoma , 2015, NeuroImage.

[122]  Sébastien Ourselin,et al.  In vivo imaging of tau pathology using multi-parametric quantitative MRI , 2015, NeuroImage.

[123]  A. Martinos,et al.  Fast simulation and optimization of pulse-train chemical exchange saturation transfer (CEST) imaging , 2015 .

[124]  Edward A. Randtke,et al.  Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm. , 2016, Journal of magnetic resonance.

[125]  David C Alsop,et al.  Amide proton transfer imaging with improved robustness to magnetic field inhomogeneity and magnetization transfer asymmetry using saturation with frequency alternating RF irradiation , 2011, Magnetic resonance in medicine.

[126]  Kyle M. Jones,et al.  Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI , 2017, Molecular Imaging and Biology.

[127]  R. Bryant,et al.  The dynamics of water-protein interactions. , 1996, Annual review of biophysics and biomolecular structure.

[128]  P. Z. Sun,et al.  A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST-EPI) steady state solution and the CEST sensitivity efficiency-based optimization approach. , 2016, Contrast media & molecular imaging.

[129]  Bennett A Landman,et al.  Development of chemical exchange saturation transfer at 7T , 2011, Magnetic resonance in medicine.

[130]  Kenya Murase,et al.  Numerical solutions to the time-dependent Bloch equations revisited. , 2011, Magnetic resonance imaging.

[131]  Benjamin N. Conrad,et al.  Chemical exchange saturation transfer of the cervical spinal cord at 7 T , 2016, NMR in biomedicine.

[132]  Mark F. Lythgoe,et al.  In vivo imaging of glucose uptake and metabolism in tumors , 2012, Nature Medicine.

[133]  Robert Bartha,et al.  Quantitative Tissue Ph Measurement during Cerebral Ischemia Using Amine and Amide Concentration-Independent Detection (AACID) with MRI , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[134]  Nirbhay N. Yadav,et al.  CEST theranostics: label-free MR imaging of anticancer drugs , 2016, Oncotarget.

[135]  Q. Chan,et al.  Chemical Exchange Saturation Transfer (CEST) MR Technique for Liver Imaging at 3.0 Tesla: an Evaluation of Different Offset Number and an After-Meal and Over-Night-Fast Comparison , 2016, Molecular Imaging and Biology.

[136]  Leif Østergaard,et al.  Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI , 2014, NMR in biomedicine.

[137]  S. Holland,et al.  NMR relaxation times in the human brain at 3.0 tesla , 1999, Journal of magnetic resonance imaging : JMRI.

[138]  Dong-Hoon Lee,et al.  Accelerating chemical exchange saturation transfer (CEST) MRI by combining compressed sensing and sensitivity encoding techniques , 2017, Magnetic resonance in medicine.

[139]  Jinyuan Zhou,et al.  Three‐dimensional amide proton transfer MR imaging of gliomas: Initial experience and comparison with gadolinium enhancement , 2013, Journal of magnetic resonance imaging : JMRI.