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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]. As the exchange rate must be smaller than the chemical shift, the increased spectral dispersion allows for faster exchanging compounds to be detected [8].
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 [8,9]. The same group also investigated phosphocreatine (PCr) modulation with PCrCEST in the hindlimb of mice and found a 29% higher PCrCEST signal at 15.2 Tesla than at 9.4 Tesla. The significant sensitivity of PCrCEST in hindlimb indicates that PCrCEST could be valuable for mapping energy metabolism in muscles such as the heart [10].
A prominent CEST application which benefits from UHF is GluCEST, which monitors local metabolic defects in neurodegenerative diseases [6,11]. 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 [11], 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 [12].
Furthermore, there are indications that glucoCEST can be used to investigate metabolism associated with neuronal activity. GlucoCEST performed at 17.2 Tesla using a rat model of electrical forepaw stimulation showed negative contrast during stimulation in the same regions that BOLD imaging provided positive contrast, thus demonstrating the ability of CEST fMRI to locally monitor temporal changes of glucose concentration [13].

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] Wu B, Warnock G, Zaiss M, Lin C, Chen M, Zhou Z, Mu L, Nanz D, Tuura R, Delso G. An overview of CEST MRI for non-MR physicists. 2016; EJNMMI Physics 3:19
www.ncbi.nlm.nih.gov/pubmed/27562024
[9] 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
[10] Chung JJ, Jin T, Lee JH, Kim SG. Chemical exchange saturation transfer imaging of phosphocreatine in the muscle.  Magnetic Resonance in Medicine 2019, 81(6):3476-3487. doi: 10.1002/mrm.27655
www.ncbi.nlm.nih.gov/pubmed/30687942
[11] 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
[12] 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
[13] Roussel T, Frydman L, Le Bihan D, Ciobanu L. Brain sugar consumption during neuronal activation detected by CEST functional MRI at ultra-high magnetic fields. Scientific Reports 9(1):4423. doi.org/10.1038/s41598-019-40986-9 1
www.ncbi.nlm.nih.gov/pubmed/30872689