The Macromolecular MR Spectrum in Healthy Aging

Hui, S.; Gong, T.; Zoellner, H. J.; Song, Y.; Murali-Manohar, S.; Oeltzschner, G.; Mikkelsen, M.; Tapper, S.; Chen, Y.; Saleh, M.; Porges, E. C.; Chen, W.; Wang, G.; Edden, R. A. E.

doi:10.1101/2021.08.27.457961

bioRxiv · 10.1101/2021.08.27.457961

The Macromolecular MR Spectrum in Healthy Aging

Hui, S.·Gong, T.·Zoellner, H. J.·Song, Y.·Murali-Manohar, S.·Oeltzschner, G.·Mikkelsen, M.·Tapper, S.·Chen, Y.·Saleh, M.·Porges, E. C.·Chen, W.·Wang, G.·Edden, R. A. E.

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Abstract

PurposeMobile macromolecules (MMs) from amino acids, cytosolic proteins and mobile lipids contribute a significant spectral background underlying the metabolite signals in the MR spectrum. A recent consensus recommends that MM contributions should be removed or included in modeling basis sets for determination of metabolite concentrations and/or metabolite ratios. The purpose of this study was to acquire the MM spectrum from healthy participants at a range of ages, and to investigate changes in the signals with age and sex groups. MethodsInversion time (TI) series were acquired to determine an optimal inversion time to null the metabolite signals. Experiments were carried out using a single adiabatic hyperbolic-secant inversion pulse. After the preliminary experiment, 102 volunteers (49M/53F) between 20 and 69 years were recruited for in vivo data acquisition in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). The protocol consisted of a T1-weighted MPRAGE for structural images, followed by PRESS localization using a voxel size of 30 x 26 x 26 mm3 with pre-inversion (TR/TI 2000/600 ms) and CHESS water suppression. Metabolite-nulled spectra were modeled using a reduced basis set (NAA, Cr, Cho, Glu) and a flexible spline baseline (0.1 ppm knot spacing) followed by subtraction of the modeled metabolite signals to yield a clean MM spectrum, using the Osprey software. Pearsons correlation coefficient was calculated between integrals and age for the 14 MM signals between 0.9-4.2 ppm. One-way ANOVA was performed to determine differences between age groups. An independent t-test was carried out to determine differences between sexes. Relationships between brain tissues with age and sex groups were also measured. ResultsMM spectra were successfully acquired in 99 (CSO) and 96 (PCC) of 102 subjects. No significant correlations were seen between age and MM integrals. One-way ANOVA also suggested no age-group differences for any MM peak (all p > 0.004). No differences were observed between sex groups. The voxels were segmented as 80 {+/-} 4% white matter, 18 {+/-} 4% gray matter, and 2 {+/-} 1% CSF for CSO and 28 {+/-} 4% white matter, 61 {+/-} 4% gray matter and 11 {+/-} 1% CSF for PCC. WM and GM showed a significant (p < 0.05) negative linear association with age in the WM-predominant CSO (R = -0.29) and GM-predominant PCC regions (R = -0.57) respectively while CSF increased significantly with age in both regions. ConclusionOur findings indicate that the MM spectrum is stable across a large age range and between sexes, suggesting a pre-defined MM basis function can be used for linear combination modeling of metabolite data from different age and sex groups. HighlightsO_LIA large publicly available MM-aging dataset is presented. C_LIO_LIMacromolecule signals do not change with age between 20 and 70. C_LIO_LIThere is no sex difference for macromolecule integrals. C_LI

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Hui, S., Gong, T., Zoellner, H. J., Song, Y., Murali-Manohar, S., Oeltzschner, G., Mikkelsen, M., Tapper, S., Chen, Y., Saleh, M., Porges, E. C., Chen, W., Wang, G., Edden, R. A. E.. 2021-08-28. The Macromolecular MR Spectrum in Healthy Aging. https://doi.org/10.1101/2021.08.27.457961

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