Transfer von Parawasserstoff induzierter Kernspinpolarisation auf 13C zur Empfindlichkeitssteigerung in der Magnetresonanztomographie
Final Report Abstract
Bernarding group. The first focus was the implementation and optimization of the technical environment and the workflows for PHIP NMR. A mobile para-hydrogen-enriching unit was built allowing PHIP in different labs. A new 300 MHz NMR spectrometer (Bruker WB 300) was installed and, in close cooperation with the Bommerich group the protocols for PHIP (1H and hetero nuclei) were developed and optimized for the 300 MHz spectrometer and the experimental MR tomograph located at LIN (Bruker, 4.7T). In cooperation with the Bommerich group the Bernarding group simulated, optimized and built a 1H/13C surface coil. To test 13C PHIP image protocols an angiography phantom was developed. The second focus was the development of novel hyperpolarized 19F labeled molecules to serve as background-free detection of biomarkers. In close cooperation with the Bommerich group that had so far published the only existing para-hydrogen hyperpolarized 19F spectrum 3-fluorstyrene was successfully hyperpolarized which led to the first hyperpolarized 19F image while the thermally polarized image did not allow to detect any 19F signal. Signal enhancement (under ALTADENA condition) for 19F was highest in the meta position. To move towards biocompatible substances 19F-labeled semi-fluorinated carbons (PFC) were studied as some PFC are certified already since a long time for medical use. Surprisingly, the signal enhancement with a factor of about 20 was highest when 19F was not vicinal to the position of the hydrogenation site but on the terminal CF3 group. Relaxation times were comparable for all positions leaving the transfer mechanism of the hyperpolarization from 1H to 19F over 8-9 bonds an open question to be solved in the next period of the project. In cooperation with the Bommerich group a fluorinated substance could be hyperpolarized on 19F that has strong structural similarities to biomarkers used for Alzheimer imaging (see below). In the next study PHIP was applied to hyperpolarize ethanol which until now was not achieved as the unsaturated precursor of ethanol exhibits a keto-enol-tautomerism rendering the molecular configuration instable. In a new approach the enol form was stabilized in ester configuration followed by hydrogenation and subsequent hydrolysis of the according carbon acid which finally yielded hyperpolarized ethanol for the first time. This working package was done in close cooperation with the Bommerich group. In the last part PHIP was explored as a means to increase the SNR in low or ultra-low fields. PHIP allowed to detect both 1H and 19F resonances simultaneously with only one scan in Ethyl 4,4,4-trifluorcrotonate which was reported before only by Hamans et al. ( 2011). For increasing the sensitivity for simultaneous broadband detection of several hetero nuclei in varying low fields (earth field and less) a SQUID-based detection unit was constructed by the Bernarding WG and realized with support of the Physikalisch-Technische Bundesanstalt, Berlin. Due to delivery problems of the dewar the time line of this sub-project was delayed but the detection, polarization, and fieldcompensation unit were realized. Extensive noise measurements within and outside magnetically and electromagnetically shielded rooms showed that operating a SQUID in environments outside a shielded room is possible by using a 0.2 mm thick aluminum foil but at the cost of a severely decreased signal-tonoise ratio.
Publications
- Para-hydrogen induced polarization in homogenous phase – an example how ionic liquids affect homogenization and thus activation of catalysts. Phys. Chem. Chem. Phys., 11, (2009), 9170–9175
T. Gutmann, M. Sellin, H. Breitzke, A. Stark, G. Buntkowsky
- Hyperpolarized 19F-MRI: para-hydrogen induced polarization and field variation enabling 19F-MRI at low spin density. Phys.Chem.Chem.Phys., 12, (2010), 10309-10312
U. Bommerich, T. Trantzschel, S. Mulla-Osman, G. Buntkowsky, J. Bargon, J. Bernarding
- Understanding the leaching Properties of heterogenized Catalysts: a combined Solid-State and PHIP NMR Study. Solid-State NMR., 38, (2010), 90-96
T. Gutmann; T. Ratajczyk; Y. Xu; H. Breitzke; A. Gruenberg; S. Dillenberger; U. Bommerich; Th. Trantzschel; J. Bernarding, G. Buntkowsky
- New investigations of technical rhodium and iridium catalysts in homogeneous phase employing Para-Hydrogen Induced Polarization.Solid-State NMR.,40, (2011), 88–90
T. Gutmann, T. Ratajczyk, S. Dillenberger, Y. Xu, A. Grünberg, H. Breitzke, U. Bommerich, T. Trantzschel, J. Bernarding, G. Buntkowsky
- Para-hydrogen induced polarization in face of ketoenoltautomerism: proof of concept with hyperpolarized ethanol. Phys. Chem. Chem. Phys., 14, (2012), 5601-5604
Th. Trantzschel, J. Bernarding, M. Plaumann, D. Lego, T. Gutmann, T. Ratajczyk, S. Dillenberger, G. Buntkowsky, J. Bargon, U. Bommerich
(See online at https://doi.org/10.1039/c2cp40272f) - Time Domain Para-Hydrogen Induced Polarization. Solid-State NMR., 43-44, (2012), 14-21
T. Ratajczyk, T. Gutmann, S. Dillenberger, S. Abdulhussaein, J. Frydel, H. Breitzke, U. Bommerich, Th. Trantzschel, J. Bernarding, P. Magusin, G. Buntkowsky
(See online at https://doi.org/10.1016/j.ssnmr.2012.02.002) - Application of Para-hydrogen Induced Polarization to Unprotected Dehydroamino Carboxylic Acids. Appl. Magn. Res., 44, (2013), 267-278
Th. Trantzschel, M. Plaumann, J.Bernarding, D.Lego, T. Ratajczyk, S. Dillenberger, G. Buntkowsky, J. Bargon, U. Bommerich
(See online at https://doi.org/10.1007/s00723-012-0391-0) - NMR Studies of the Reaction Path of the o-H2/p-H2 Spin Conversion Catalyzed by Vaska's Complex in the Solid-State; Appl. Magn. Res., 44, (2013), 247-265
J. Matthes, S. Gründemann, G. Buntkowsky, B. Chaudret, H.-H. Limbach
(See online at https://doi.org/10.1007/s00723-012-0395-9) - Parahydrogen-Induced Polarization Transfer to 19F in Perfluorocarbons for 19F NMR and MRI. Chem. Eur. J. 19, 6334 – 6339
M. Plaumann, U. Bommerich, T. Trantzschel, D. Lego, S. Dillenberger, G. Sauer, J. Bargon, G. Buntkowsky, J. Bernarding
- PHIP-Label: Parahydrogen-Induced Polarization in Propargylglycine-Containing Synthetic Oligopeptides, Chem.Comm. (2013), 49,7839-7841
M. Tischler, G. Sauer, A.Heil, D. Nasu, M. Empting, D. Tietze, S. Voigt, H. Weidler, T. Gutmann, O. Avrutina, H. Kolmar, T. Ratajczyk, G. Buntkowsky
(See online at https://doi.org/10.1039/c3cc43978j) - Parahydrogen-induced polarization of carboxylic acids: a pilot study of valproic acid and related structures. NMR Biomed., (2014), 27, 810 – 816
D. Lego, M.Plaumann ,T.Trantzschel, J. Bargon, H. Scheich, G. Buntkowsky, T. Gutmann, G. Sauer, J. Bernarding, U. Bommerich
(See online at https://doi.org/10.1002/nbm.3123) - Synthesis, Solid State NMR-Characterization and Application of a novel Wilkinson’s type immobilized Catalyst for hydrogenation reactions, Chemistry Eur.J., (2014), 20, 1159-1166
S. Abdulhussain, H. Breitzke, T. Ratajczyk, A. Grünberg, M. Srour, D. Arnaut, H. Weidler, U. Kunz, H.J. Kleebe, U. Bommerich, J. Bernarding, T. Gutmann, G. Buntkowsky
(See online at https://doi.org/10.1002/chem.201303020)
