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Ultra High Field - Capitalizing on Higher Spectral Dispersion

Spectroscopy

Due to the increased sensitivity and high spectral dispersion at Ultra High Field (UHF), a natural UHF application is magnetic resonance spectroscopy (MRS). Commercially available MRS instruments are readily available today with field strengths up to 23.5 Tesla, allowing ultra-high resolution spectroscopy experiments of small samples [1].

Similarly, UHF MRI magnets can exploit the increased chemical shift and sensitivity in vivo. Thus, significant improvements in preclinical in vivo MRS have been reported when using UHF magnets [2,3,4,5]. Notably, it has been shown that certain metabolites could be detected for the first time in vivo due to the high magnetic field strength [4].

Beyond the benefits in sensitivity gain and high chemical shift, it could be further shown that a relaxation enhanced MRS strategy allows to additionally utilize the difference in relaxation times between water and metabolites at UHF to generate “water-free” MRS without the need for common water suppression techniques [3].

Exemplary in vivo mouse spectrum acquired at 15.2 Tesla with the MRI CryoProbe

Exemplary in vivo mouse spectrum acquired at 15.2 Tesla with an MRI CryoProbe. A & B) Anatomical reference with indicated voxel position. C) Corresponding spectrum. Method: STEAM, Echo Time: 1.1 ms, Voxel Size: (2 x 2 x 2) mm³, Resolution enhancement with shifted Gauss filtering, Shift: 7%, Broadening: 7 Hz, Scan time: 17 min.

References:

[1] Overview Aeon 1GHz | Bruker: www.bruker.com/products/mr/nmr/magnets/magnets/aeon-1ghz/overview
[2] Öz G, Tkáč I, Uğurbil K. Animal models and high field imaging and spectroscopy. Dialogues in Clinical Neuroscience. 2013;15(3):263-278.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3811099/
[3] Shemesh N, Rosenberg JT, Dumez J-N, Muniz JA, Grant SC, Frydman L. Metabolic properties in stroked rats revealed by relaxation-enhanced magnetic resonance spectroscopy at ultrahigh fields. Nat Commun. 2014; 5: 4958. doi: 10.1038/ncomms5958
www.ncbi.nlm.nih.gov/pubmed/25229942
[4] Mlynárik V, Cudalbu C, Xin L, Gruetter R. 1H NMR spectroscopy of rat brain in vivo at 14.1Tesla: improvements in quantification of the neurochemical profile. J Magn Reson. 2008; 194: 163–168. doi: 10.1016/j.jmr.2008.06.019
www.ncbi.nlm.nih.gov/pubmed/18703364
[5] Shemesh N, Rosenberg JT, Dumez J-N, Grant SC, Frydman L. Metabolic T1 dynamics and longitudinal relaxation enhancement in vivo at ultrahigh magnetic fields on ischemia. Journal of Cerebral Blood Flow 2014;34(11):1810-1817. doi:10.1038/jcbfm.2014.149.
www.ncbi.nlm.nih.gov/pmc/articles/PMC4269758/

Chemical Exchange MRI

In addition to spectroscopy, the increased spectral dispersion also benefits magnetization transfer techniques such as Chemical Exchange Saturation Transfer (CEST) imaging, leading to a high selectivity [6]. Further advantages of chemical exchange techniques at UHF include the higher saturation which can be achieved [6] and a reduction of the exchange rate relative to the chemical shift [7]. 
A recent paper from Chung et al. demonstrated a significantly increased chemical exchange effect for the amine proton signal in rat brain at 15.2 Tesla compared to 9.4 Tesla. An increase of 65% compared to 9.4 Tesla was reported emphasizing the importance of UHF for chemical exchange applications [7,8].
A prominent CEST application which benefits from UHF is GluCEST, which monitors local metabolic defects in neurodegenerative diseases [6,9]. For example, GluCEST was identified in the past to be a potential in vivo biomarker of Huntington’s disease when applied in a knock-in mouse model using UHF [9], and has recently been used in a mouse epilepsy model, in which chronically methionine sulfoximine (MSO)-seizure-inducing treated mice showed reduced GluCEST contrast in the hippocampus [10].

References:

[6] Metabolic Imaging in Neurodegenerative Disease using CEST MRI | Bruker: www.bruker.com/service/education-training/webinars/pci-webinars
[7] Chung JJ, Choi W, Jin T, Lee JH, Kim S-G. Chemical-exchange-sensitive MRI of amide, amine and NOE at 9.4 T versus 15.2 T. NMR in Biomedicine. 2017;30:e3740. doi.org/10.1002/nbm.3740
www.ncbi.nlm.nih.gov/pubmed/28544035
[8] New insights into brain function with molecular and functional MRI of the rodent brain at ultra-high fields | Bruker:
www.bruker.com/service/education-training/webinars/pci-webinars
[9] Pépin J, Francelle L, Carrillo-de Sauvage M-A, de Longprez L, Gipchtein P, Cambon K, Valette J, Brouillet E, Flament J. In vivo imaging of brain glutamate defects in a knock-in mouse model of Huntington's disease. Neuroimage. 2016; 139: 53–64. doi: 10.1016/j.neuroimage.2016.06.023
www.ncbi.nlm.nih.gov/pubmed/27318215
[10] Bagga P, Pickup S, Flament J, Detre J, Hariharan H, Reddy R. Mapping astroglial glutamine synthetase activity in vivo in a preclinical model of epilepsy using glutamate-weighted CEST (GluCEST) MRI. ISMRM 2019 3121
https://index.mirasmart.com/ISMRM2019/PDFfiles/3121.html