Keywords: Cest, Contrast Media, Iodinated Contrast Media, Pulsed-Cest, Radiographic Agents, Train Pulses, Magnetic Resonance Imaging, Ph Sensors, Chemical Exchange, Chemical Exchange Saturation Transfer, Clinical Scanners, Physiological Range,
Affiliations: *** IBB - CNR ***
Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Universita degli Studi di Torino, Torino, Italy., CRB Bracco Imaging S.p.A., Via Ribes 5, Colleretto Giacosa (TO), Italy., Department of High-field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tubingen, Germany., Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Universita degli Studi di Torino, Torino, Italy; Consiglio Nazionale delle Ricerche (CNR), Istituto di Biostrutture e Bioimmagini, Torino, Italy. Electronic address: dario.longo@unito.it.,
References: van Zijl, P.C., Yadav, N.N., Chemical exchange saturation transfer (CEST): what is in a name and what isn't? (2011) Magn. Reson. Med., 65, pp. 927-94
Liu, G., Song, X., Chan, K.W., McMahon, M.T., Nuts and bolts of chemical exchange saturation transfer MRI (2013) NMR Biomed., 26, pp. 810-828
Vinogradov, E., Sherry, A.D., Lenkinski, R.E., CEST: from basic principles to applications, challenges and opportunities (2013) J. Magn. Reson., 229, pp. 155-172
Jones, C.K., Schlosser, M.J., van Zijl, P.C., Pomper, M.G., Golay, X., Zhou, J., Amide proton transfer imaging of human brain tumors at 3T (2006) Magn. Reson. Med., 56, pp. 585-592
van Zijl, P.C., Jones, C.K., Ren, J., Malloy, C.R., Sherry, A.D., MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST) (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 4359-4364
Nasrallah, F.A., Pages, G., Kuchel, P.W., Golay, X., Chuang, K.H., Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI (2013) J. Cereb. Blood Flow Metab., 33, pp. 1270-1278
Rivlin, M., Horev, J., Tsarfaty, I., Navon, G., Molecular imaging of tumors and metastases using chemical exchange saturation transfer (CEST) MRI (2013) Sci. Rep., 3, p. 3045
Delli Castelli, D., Terreno, E., Aime, S., Yb(III)-HPDO3A: a dual pH- and temperature-responsive CEST agent (2011) Angew. Chem. Int. Ed. Engl., 50, pp. 1798-1800
Dastru, W., Longo, D., Aime, S., Contrast agents and mechanisms (2011) Drug Discov. Today: Technol., 8, pp. e109-e115
Wang, X., Wu, Y., Soesbe, T.C., Yu, J., Zhao, P., Kiefer, G.E., Sherry, A.D., A pH-responsive MRI agent that can be activated beyond the tissue magnetization transfer window (2015) Angew. Chem. Int. Ed. In Engl., 54, pp. 8662-8664
Rivlin, M., Navon, G., Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors (2016) Sci. Rep., 6, p. 32648
Rivlin, M., Tsarfaty, I., Navon, G., Functional molecular imaging of tumors by chemical exchange saturation transfer MRI of 3-O-Methyl-D-glucose (2014) Magn. Reson. Med., 72, pp. 1375-1380
Bar-Shir, A., Bulte, J.W., Gilad, A.A., Molecular engineering of nonmetallic biosensors for CEST MRI (2015) ACS Chem. Biol., 10, pp. 1160-1170
Sun, P.Z., Zhou, J., Huang, J., van Zijl, P., Simplified quantitative description of amide proton transfer (APT) imaging during acute ischemia (2007) Magn. Reson. Med., 57, pp. 405-410
Zaiss, M., Windschuh, J., Paech, D., Meissner, J.E., Burth, S., Schmitt, B., Kickingereder, P., Radbruch, A., Relaxation-compensated CEST-MRI of the human brain at 7T: unbiased insight into NOE and amide signal changes in human glioblastoma (2015) Neuroimage, 112, pp. 180-188
Longo, D.L., Moustaghfir, F.Z., Zerbo, A., Consolino, L., Anemone, A., Bracesco, M., Aime, S., EXCI-CEST: exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging (2017) Int. J. Pharmaceut., 525, pp. 275-281
Ferrauto, G., Delli Castelli, D., Di Gregorio, E., Langereis, S., Burdinski, D., Grull, H., Terreno, E., Aime, S., Lanthanide-loaded erythrocytes as highly sensitive chemical exchange saturation transfer MRI contrast agents (2014) J. Am. Chem. Soc., 136, pp. 638-641
Liu, G., Bettegowda, C., Qiao, Y., Staedtke, V., Chan, K.W., Bai, R., Li, Y., van Zijl, P.C., Noninvasive imaging of infection after treatment with tumor-homing bacteria using Chemical Exchange Saturation Transfer (CEST) MRI (2013) Magn. Reson. Med., 70, pp. 1690-1698
Longo, D.L., Di Gregorio, E., Abategiovanni, R., Ceccon, A., Assfalg, M., Molinari, H., Aime, S., Chemical exchange saturation transfer (CEST): an efficient tool for detecting molecular information on proteins' behaviour (2014) Analyst, 139, pp. 2687-2690
Ceccon, A., D'Onofrio, M., Zanzoni, S., Longo, D.L., Aime, S., Molinari, H., Assfalg, M., NMR investigation of the equilibrium partitioning of a water-soluble bile salt protein carrier to phospholipid vesicles (2013) Proteins, 81, pp. 1776-1791
Zaiss, M., Kunz, P., Goerke, S., Radbruch, A., Bachert, P., MR imaging of protein folding in vitro employing nuclear-Overhauser-mediated saturation transfer (2013) NMR Biomed., 26, pp. 1815-1822
Cai, K., Haris, M., Singh, A., Kogan, F., Greenberg, J.H., Hariharan, H., Detre, J.A., Reddy, R., Magnetic resonance imaging of glutamate (2012) Nat. Med., 18, pp. 302-306
Kogan, F., Haris, M., Singh, A., Cai, K., Debrosse, C., Nanga, R.P., Hariharan, H., Reddy, R., Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer (2014) Magn. Reson. Med., 71, pp. 164-172
Tsitovich, P.B., Burns, P.J., McKay, A.M., Morrow, J.R., Redox-activated MRI contrast agents based on lanthanide and transition metal ions (2014) J. Inorgan. Biochem., 133, pp. 143-154
Funk, A.M., Clavijo Jordan, V., Sherry, A.D., Ratnakar, S.J., Kovacs, Z., Oxidative conversion of a Europium(II)-based T1 agent into a Europium(III)-Based paraCEST agent that can be detected in vivo by magnetic resonance imaging (2016) Angew. Chem. Int. Ed. In Engl., 55, pp. 5024-5027
Bar-Shir, A., Liu, G., Greenberg, M.M., Bulte, J.W., Gilad, A.A., Synthesis of a probe for monitoring HSV1-tk reporter gene expression using chemical exchange saturation transfer MRI (2013) Nat. Protoc., 8, pp. 2380-2391
Liu, G., Liang, Y., Bar-Shir, A., Chan, K.W., Galpoththawela, C.S., Bernard, S.M., Tse, T., Gilad, A.A., Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent (2011) J. Am. Chem. Soc., 133, pp. 16326-16329
Aime, S., Delli Castelli, D., Terreno, E., Novel pH-reporter MRI contrast agents (2002) Angew. Chem. Int. Ed. Engl., 41, pp. 4334-4336
Geraldes, C.F., Laurent, S., Classification and basic properties of contrast agents for magnetic resonance imaging (2009) Contrast Media Mol. Imag., 4, pp. 1-23
Hingorani, D.V., Bernstein, A.S., Pagel, M.D., A review of responsive MRI contrast agents: 2005–2014 (2015) Contrast Media Mol. Imag., 10, pp. 245-265
Longo, D.L., Dastru, W., Digilio, G., Keupp, J., Langereis, S., Lanzardo, S., Prestigio, S., Aime, S., 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) Magn. Reson. Med., 65, pp. 202-211
Longo, D.L., Busato, A., Lanzardo, S., Antico, F., Aime, S., Imaging the pH evolution of an acute kidney injury model by means of iopamidol, a MRI-CEST pH-responsive contrast agent (2013) Magn. Reson. Med., 70, pp. 859-864
Longo, D.L., Bartoli, A., Consolino, L., Bardini, P., Arena, F., Schwaiger, M., Aime, S., In vivo imaging of tumor metabolism and acidosis by combining PET and MRI-CEST pH imaging (2016) Cancer Res., 76, pp. 6463-6470
Longo, D.L., Cutrin, J.C., Michelotti, F., Irrera, P., Aime, S., Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST-MRI (2017) NMR Biomed., 30
Chen, L.Q., Howison, C.M., Jeffery, J.J., Robey, I.F., Kuo, P.H., Pagel, M.D., Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI (2014) Magn. Reson. Med., 72, pp. 1408-1417
Yang, X., Song, X., Ray Banerjee, S., Li, Y., Byun, Y., Liu, G., Bhujwalla, Z.M., McMahon, M.T., Developing imidazoles as CEST MRI pH sensors (2016) Contrast Media Mol. Imag., 11, pp. 304-312
Ward, K.M., Balaban, R.S., Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST) (2000) Magn. Reson. Med., 44, pp. 799-802
Longo, D.L., Sun, P.Z., Consolino, L., Michelotti, F.C., Uggeri, F., Aime, S., A general MRI-CEST ratiometric approach for pH imaging: demonstration of in vivo pH mapping with lobitridol (2014) J. Am. Chem. Soc., 136, pp. 14333-14336
Sun, P.Z., Benner, T., Kumar, A., Sorensen, A.G., Investigation of optimizing and translating pH-sensitive pulsed-chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner (2008) Magn. Reson. Med., 60, pp. 834-841
Schmitt, B., Zaiss, M., Zhou, J., Bachert, P., Optimization of pulse train presaturation for CEST imaging in clinical scanners (2011) Magn. Reson. Med., 65, pp. 1620-1629
Sun, P.Z., Wang, E., Cheung, J.S., Zhang, X., Benner, T., Sorensen, A.G., 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) Magn. Reson. Med., 66, pp. 1042-1048
Meissner, J.E., Goerke, S., Rerich, E., Klika, K.D., Radbruch, A., Ladd, M.E., Bachert, P., Zaiss, M., Quantitative pulsed CEST-MRI using Omega-plots (2015) NMR Biomed., 28, pp. 1196-1208
Yoshimaru, E.S., Randtke, E.A., Pagel, M.D., Cardenas-Rodriguez, J., Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm (2016) J. Magn. Reson., 263, pp. 184-192
Tee, Y.K., Khrapitchev, A.A., Sibson, N.R., Payne, S.J., Chappell, M.A., Evaluating the use of a continuous approximation for model-based quantification of pulsed chemical exchange saturation transfer (CEST) (2012) J. Magn. Reson., 222, pp. 88-95
Desmond, K.L., Stanisz, G.J., Understanding quantitative pulsed CEST in the presence of MT (2012) Magn. Reson. Med., 67, pp. 979-990
Roeloffs, V., Meyer, C., Bachert, P., Zaiss, M., Towards quantification of pulsed spinlock and CEST at clinical MR scanners: an analytical interleaved saturation-relaxation (ISAR) approach (2015) NMR Biomed., 28, pp. 40-53
Jones, C.K., Polders, D., Hua, J., Zhu, H., Hoogduin, H.J., Zhou, J., Luijten, P., van Zijl, P.C., In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T (2012) Magn. Reson. Med., 67, pp. 1579-1589
Desmond, K.L., Mehrabian, H., Chavez, S., Sahgal, A., Soliman, H., Rola, R., Stanisz, G.J., Chemical exchange saturation transfer for predicting response to stereotactic radiosurgery in human brain metastasis (2016) Magn. Reson. Med.
Stabinska, J., Cronenberg, T., Wittsack, H.J., Lanzman, R.S., Muller-Lutz, A., Quantitative pulsed CEST-MRI at a clinical 3T MRI system (2017) MAGMA
Zu, Z., Li, K., Janve, V.A., Does, M.D., Gochberg, D.F., Optimizing pulsed-chemical exchange saturation transfer imaging sequences (2011) Magn. Reson. Med., 66, pp. 1100-1108
Zu, Z., Janve, V.A., Li, K., Does, M.D., Gore, J.C., Gochberg, D.F., Multi-angle ratiometric approach to measure chemical exchange in amide proton transfer imaging (2012) Magn. Reson. Med., 68, pp. 711-719
Sun, P.Z., Simplified and scalable numerical solution for describing multi-pool chemical exchange saturation transfer (CEST) MRI contrast (2010) J. Magn. Reson., 205, pp. 235-241
Woessner, D.E., Zhang, S., Merritt, M.E., Sherry, A.D., Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI (2005) Magn. Reson. Med., 53, pp. 790-799
Sun, P.Z., Longo, D.L., Hu, W., Xiao, G., Wu, R., Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH (2014) Phys. Med. Biol., 59, pp. 4493-4504
Longo, D.L., Michelotti, F., Consolino, L., Bardini, P., Digilio, G., Xiao, G., Sun, P.Z., Aime, S., In vitro and in vivo assessment of nonionic iodinated radiographic molecules as chemical exchange saturation transfer magnetic resonance imaging tumor perfusion agents (2016) Invest. Radiol., 51, pp. 155-162
Ramani, A., Dalton, C., Miller, D.H., Tofts, P.S., Barker, G.J., Precise estimate of fundamental in-vivo MT parameters in human brain in clinically feasible times (2002) Magn. Reson. Imag., 20, pp. 721-731
Stancanello, J., Terreno, E., Castelli, D.D., Cabella, C., Uggeri, F., Aime, S., Development and validation of a smoothing-splines-based correction method for improving the analysis of CEST-MR images (2008) Contrast Media Mol. Imag., 3, pp. 136-149
Anemone, A., Consolino, L., Longo, D.L., MRI-CEST assessment of tumour perfusion using X-ray iodinated agents: comparison with a conventional Gd-based agent (2017) Eur. Radiol., 27, pp. 2170-2179
Woods, M., Woessner, D.E., Sherry, A.D., Paramagnetic lanthanide complexes as PARACEST agents for medical imaging (2006) Chem. Soc. Rev., 35, pp. 500-511
Sherry, A.D., Wu, Y., The importance of water exchange rates in the design of responsive agents for MRI (2013) Curr. Opin. Chem. Biol, 17, pp. 167-174
Khlebnikov, V., Geades, N., Klomp, D.W.J., Hoogduin, H., Gowland, P., Mougin, O., Comparison of pulsed three-dimensional CEST acquisition schemes at 7 tesla: steady state versus pseudosteady state (2017) Magn. Reson. Med., 77, pp. 2280-2287
Ward, K.M., Aletras, A.H., Balaban, R.S., A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST) (2000) J. Magn. Reson., 143, pp. 79-87
Moon, B.F., Jones, K.M., Chen, L.Q., Liu, P., Randtke, E.A., Howison, C.M., Pagel, M.D., A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH (2015) Contrast Media Mol. Imag., 10, pp. 446-455
Wu, R., Longo, D.L., Aime, S., Sun, P.Z., Quantitative description of radiofrequency (RF) power-based ratiometric chemical exchange saturation transfer (CEST) pH imaging (2015) NMR Biomed., 28, pp. 555-565
Wu, Y., Zhang, S., Soesbe, T.C., Yu, J., Vinogradov, E., Lenkinski, R.E., Sherry, A.D., pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent (2016) Magn. Reson. Med., 75, pp. 2432-2441
Tsitovich, P.B., Cox, J.M., Spernyak, J.A., Morrow, J.R., Gear up for a pH shift: a responsive Iron(II) 2-amino-6-picolyl-appended macrocyclic paraCEST agent that protonates at a pendent group (2016) Inorg. Chem., 55, pp. 12001-12010
Muller-Lutz, A., Khalil, N., Schmitt, B., Jellus, V., Pentang, G., Oeltzschner, G., Antoch, G., Wittsack, H.J., Pilot study of Iopamidol-based quantitative pH imaging on a clinical 3T MR scanner (2014) MAGMA, 27, pp. 477-485
Xu, X., Yadav, N.N., Song, X., McMahon, M.T., Jerschow, A., van Zijl, P.C., Xu, J., Screening CEST contrast agents using ultrafast CEST imaging (2016) J. Magn. Reson., 265, pp. 224-229
Dopfert, J., Zaiss, M., Witte, C., Schroder, L., Ultrafast CEST imaging (2014) J. Magn. Reson., 243, pp. 47-53
Varma, G., Lenkinski, R.E., Vinogradov, E., Keyhole chemical exchange saturation transfer (2012) Magn. Reson. Med., 68, pp. 1228-1233
Windschuh, J., Zaiss, M., Meissner, J.E., Paech, D., Radbruch, A., Ladd, M.E., Bachert, P., Correction of B1-inhomogeneities for relaxation-compensated CEST imaging at 7 T (2015) NMR Biomed., 28, pp. 529-537
Tse, D.H.Y., da Silva, N.A., Poser, B.A., Shah, N.J., B1+ inhomogeneity mitigation in CEST using parallel transmission (2017) Magn. Reson. Med., 78, pp. 2216-2225
Flip-angle based ratiometric approach for pulsed CEST-MRI pH imaging
Several molecules have been exploited for developing MRI pH sensors based on the chemical exchange saturation transfer (CEST) technique. A ratiometric approach, based on the saturation of two exchanging pools at the same saturation power, or by varying the saturation power levels on the same pool, is usually needed to rule out the concentration term from the pH measurement. However, all these methods have been demonstrated by using a continuous wave saturation scheme that limits its translation to clinical scanners. This study shows a new ratiometric CEST-MRI pH-mapping approach based on a pulsed CEST saturation scheme for a radiographic contrast agent (iodixanol) possessing a single chemical exchange site. This approach is based on the ratio of the CEST contrast effects at two different flip angles combinations (180 degrees /360 degrees and 180 degrees /720 degrees ), keeping constant the mean irradiation RF power (Bavg power). The proposed ratiometric approach index is concentration independent and it showed good pH sensitivity and accuracy in the physiological range between 6.0 and 7.4.
Flip-angle based ratiometric approach for pulsed CEST-MRI pH imaging
No results.
Flip-angle based ratiometric approach for pulsed CEST-MRI pH imaging