Magnetic resonance spectroscopic imaging of downfield proton resonances in the human brain at 3 T

Purpose: To extract guanidinium (Guan) and amide CEST on the human brain at 3 T MRI with the high spectral resolution (HSR) CEST combined with the polynomial Lorentzian line-shape fitting (PLOF).Methods: Continuous wave (cw) turbo spin-echo (TSE) CEST was implemented to obtain the optimum saturation parameters. Both Guan and amide CEST peaks were extracted and quantified using the PLOF method. The NMR spectra on the egg white phantoms were acquired to reveal the fitting range and the contributions to the amide and GuanCEST. Two types of CEST approaches, including cw gradient-and spin-echo (cwGRASE) and steady state EPI (ssEPI), were implemented to acquire multi-slice HSR-CEST. Results: GuanCEST can be extracted with the PLOF method at 3 T, and the optimum B 1 = 0.6 μT was determined for GuanCEST in white matter (WM) and 1.0 μT in gray matter (GM). The optimum B 1 = 0.8-1 μT was found for amide-CEST. AmideCEST is lower in both WM and GM collected with ssEPI compared to those by cwGRASE (ssEPI = [1.27-1.63]%; cwGRASE = [2.19-2.25]%). The coefficients of variation (COV) of the amide and Guan CEST in both WM and GM for ssEPI (COV: 28.6-33.4%) are significantly higher than those of cwGRASE (COV: 8.6-18.8%). Completely different WM/GM contrasts for Guan and amide CEST were observed between ssEPI and cwGRASE. The amideCEST was found to have originated from the unstructured amide protons as suggested by the NMR spectrum of the unfolded proteins in egg white. Conclusion:Guan and amide CEST mapping can be achieved by the HSR-CEST at 3 T combing with the PLOF method. K E Y W O R D Schemical exchange saturation transfer (CEST), magnetization transfer contrast (MTC), guanidinium CEST, amide CEST, continuous wave gradient-and spin-echo (cwGRASE), steady state EPI (ssEPI), polynomial Lorentzian line-shape fitting (PLOF)

Section: Discussionmentioning

confidence: 94%

Guanidinium and amide CEST mapping of human brain by high spectral resolution CEST at 3 T

Wang

Park

Kamson

et al. 2022

“…Still, APT and GluCEST are inherently limited by the relatively low spectral resolution, and their image contrast depends not only on metabolite concentration, but also on contributions from direct water saturation and magnetization transfer with semisolid tissue structures, as well as factors such as RF saturation power, B 0 heterogeneities and strength. Therefore, downfield MRS 21–34 could inform such measurements by investigating the downfield resonances with high spectral resolution (at the expense of limited spatial resolution). Our study thus sought to characterize the downfield spectrum in glioma‐bearing mice and investigate the spectral differences introduced by the tumors.…”

Section: Discussionmentioning

confidence: 99%

“…53 Still, APT and GluCEST are inherently limited by the relatively low spectral resolution, and their image contrast depends not only on metabolite concentration, but also on contributions from direct water saturation and magnetization transfer with semisolid tissue structures, as well as factors such as RF saturation power, B 0 heterogeneities and strength. Therefore, downfield MRS [21][22][23][24][25][26][27][28][29][30][31][32][33][34] could inform such measurements by investigating the downfield resonances with high…”

Section: Discussionmentioning

confidence: 99%

“…The robustness in the quantification of (tentatively assigned) NAD+ in healthy volunteers has been shown, 32 allowing the demonstration of the negative correlation between NAD+ concentration and age. Finally, recently it has been shown that magnetic resonance spectroscopic imaging can reliably map downfield resonances in the human brain at 3 T 33 …”

Section: Introductionmentioning

confidence: 99%

“…31 The robustness in the quantification of (tentatively assigned) NAD+ in healthy volunteers has been shown, 32 allowing the demonstration of the negative correlation between NAD+ concentration and age. Finally, recently it has been shown that magnetic resonance spectroscopic imaging can reliably map downfield resonances in the human brain at 3 T. 33 Image-selected-in-vivo-spectroscopy (ISIS) RE-MRS (iRE-MRS), 34 combines RE-MRS 25 with ISIS localization 35 to record spectra with short TEs (∼5 ms), enabling the characterization of broad signals in the downfield spectrum. iRE-MRS principles have since been extended to the human brain, 36,37 yielding similar downfield spectra to those presented by Gonçalves et al 34 in rat brains.…”

mentioning

confidence: 99%

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Short TE downfield magnetic resonance spectroscopy in a mouse model of brain glioma

Gonçalves

Simões

Shemesh

2022

Purpose: Enhanced cell proliferation in tumors can be associated with altered metabolic profiles and dramatic microenvironmental changes. Downfield magnetic resonance spectroscopy (MRS) has received increasing attention due to its ability to report on labile resonances of molecules not easily detected in upfield 1 H MRS. Image-selected-in-vivo-spectroscopy-relaxation enhanced MRS (iRE-MRS) was recently introduced for acquiring short echo-time (TE) spectra. Here, iRE-MRS was used to investigate in-vivo downfield spectra in glioma-bearing mice.Methods: Experiments were performed in vivo in an immunocompetent glioma mouse model at 9.4 T using a cryogenic coil. iRE-MRS spectra were acquired in N = 6 glioma-bearing mice (voxel size = 2.2 3 mm 3 ) and N = 6 control mice.Spectra were modeled by a sum of Lorentzian peaks simulating known downfield resonances, and differences between controls and tumors were quantified using relative peak areas.Results: Short TE tumor spectra exhibited large qualitative differences compared to control spectra. Most peaks appeared modulated, with strong attenuation of NAA (∼7.82, 7.86 ppm) and changes in relative peak areas between 6.75 and 8.49 ppm. Peak areas tended to be smaller for DF 6.83 , DF 7.60 , DF 8.18 and NAA; and larger for DF 7.95 and DF 8.24 . Differences were also detected in signals resonating above 8.5 ppm, assumed to arise from NAD+. Conclusions:In-vivo downfield 1 H iRE-MRS of mouse glioma revealed differences between controls and tumor bearing mice, including in metabolites which are not easily detectable in the more commonly investigated upfield spectrum.These findings motivate future downfield MRS investigations exploring pH and exchange contributions to these differences.

Identification of new resonances in downfield ¹H MRS of human calf muscle in vivo: Potentially metabolite precursors for skeletal muscle NAD⁺

Nanga

Elliott

Swain

et al. 2023

Purpose The purpose of this study was to identify and characterize newly discovered resonances appearing in the downfield proton MR spectrum (DF 1H MRS) of the human calf muscle in vivo at 7T. Methods Downfield 1H MRS was performed on the calf muscle of five healthy volunteers at 7T. A spectrally selective 90° E‐BURP RF pulse with an excitation center frequency at 10.3 ppm and an excitation bandwidth of 2 ppm was used for DF 1H MRS acquisition. Results In all participants, we observed new resonances at 9.7, 10.1, 10.3, and 10.9 ppm in the DF 1H MRS. Phantom experiments at 37°C strongly suggest the new resonance at 9.7 ppm could be from H2‐proton of the nicotinamide rings in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) while the resonance at 10.1 ppm could be attributed to the indole –NH proton of L‐tryptophan. We observed that the resonances at 10.1 and 10.9 ppm are significantly suppressed when the water resonance is saturated, indicating that these peaks have either 1H chemical exchange or cross‐relaxation with water. Conversely, the resonances at 9.7 and 10.3 ppm exhibit moderate signal reduction in the presence of water saturation. Conclusion We have identified new proton resonances in vivo in human calf muscle occurring at chemical shifts of 9.7, 10.1, 10.3, and 10.9 ppm. These preliminary results are promising for investigating the role of NR/NMN and L‐tryptophan metabolism in understanding the de novo and salvage pathways of NAD+ synthesis in skeletal muscle.