Age-Related Neurometabolic Changes and Connectivity: A Whole-Brain High-Resolution MRSI Study

Poster No:

1957 

Submission Type:

Abstract Submission 

Authors:

Wenqi Zhang1, Danni Wang1,2, Yaoyu Zhang1,3, Yibo Zhao4, Sirui Wang5, Gai Kong5, Wen Jin4,6, Yudu Li4,7,8, Huixiang Zhuang1, Bin Bo1, Yihong Yang2, Zhi-Pei Liang4,6, Yingying Tang5, Yao Li1,3

Institutions:

1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, 2Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 3Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, China, 4Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 5Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 6Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 7Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 8National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL

First Author:

Wenqi Zhang  
School of Biomedical Engineering, Shanghai Jiao Tong University
Shanghai, China

Co-Author(s):

Danni Wang  
School of Biomedical Engineering, Shanghai Jiao Tong University|Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Shanghai, China|Baltimore, MD
Yaoyu Zhang  
School of Biomedical Engineering, Shanghai Jiao Tong University|Institute of Medical Robotics, Shanghai Jiao Tong University
Shanghai, China|Shanghai, China
Yibo Zhao  
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign
Urbana, IL
Sirui Wang  
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Gai Kong  
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Wen Jin  
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, IL|Urbana, IL
Yudu Li  
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Bioengineering, University of Illinois at Urbana-Champaign|National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign
Urbana, IL|Urbana, IL|Urbana, IL
Huixiang Zhuang  
School of Biomedical Engineering, Shanghai Jiao Tong University
Shanghai, China
Bin Bo  
School of Biomedical Engineering, Shanghai Jiao Tong University
Shanghai, China
Yihong Yang  
Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health
Baltimore, MD
Zhi-Pei Liang  
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign
Urbana, IL|Urbana, IL
Yingying Tang  
Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Yao Li  
School of Biomedical Engineering, Shanghai Jiao Tong University|Institute of Medical Robotics, Shanghai Jiao Tong University
Shanghai, China|Shanghai, China

Introduction:

Alterations in neurometabolites reflect age-related structural and functional processes within the brain, including changes in metabolite concentrations as well as shifts in the balance between the primary excitatory and inhibitory neurotransmitters: glutamate (Glu) and gamma-aminobutyric acid (GABA)1.
Using proton magnetic resonance spectroscopy (¹H-MRS), previous studies have found age-related declines in N-acetylaspartate (NAA), a marker of neuronal integrity, alongside increases in myo-Inositol (mIn), an indicator of glial activity, and choline (Cho), a marker of membrane turnover2,3. Additionally, Glu and GABA exhibit dynamic developmental trajectories, with Glu increasing sharply during childhood and plateauing in adulthood, while GABA levels tend to rise with age4,5. However, these findings were based on single-voxel MRS techniques, with low spatial resolution (typically 20×20×20 mm³ voxel size), which overlook important spatial variations in metabolite distributions. Therefore, the interregional relationships of neurometabolites across the whole brain remain unexplored.
Recently, a fast, high-resolution 3D ¹H-MRSI technology, known as SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation), has enabled whole-brain mapping of multiple neurometabolites at a nominal resolution of 2×3×3 mm³ within a 10-minute scan6-10. In this study, we used SPICE to investigate age-related differences in neurometabolite concentrations and their interregional associations. Specifically, we examine seven key neurometabolites-NAA, Cho, Cr, mIn, Glu, glutamine (Gln), and GABA-across the whole brain. By characterizing age-related differences in neurometabolite concentrations and interregional neurometabolic correlations in young and mid-age adults, we aim to understand the shifts in neurometabolic organization across different ages.

Methods:

Fifty-seven healthy participants were included in this study: 30 young adults (mean age=22.20, range=15–25) and 27 mid-age adults (mean age=34.59, range=26–54). MR scans were performed on a 3T scanner at Shanghai Mental Health Center, China. Whole-brain 1H-MRSI data were obtained using the SPICE sequence (TR/TE = 1.6/160 ms, resolution = 2.0×3.0×3.0 mm³, FOV = 240×240×120 mm³). Ultrafast J-resolved MRSI data acquisition is achieved by efficiently encoding spatial, spectral, and J-coupling information with FID and dual-echo-time SE signals6. Machine learning-based method was used to reconstruct high-resolution metabolite and neurotransmitter maps from the hybrid FID/SE data7-10. The cortical regions were parcellated using Yeo 7-network atlas. Pearson correlation analyses were conducted to calculate associations with significance reserved after FDR correction. Group differences were assessed using Student's t-tests.

Results:

Figure 1A displays whole-brain neurometabolic maps averaged across young and mid-aged adult groups. Compared to young adults, the middle-aged group exhibited evidently lower levels of NAA, Cho, and Cr, along with higher levels of mIns, Glu, Gln, and GABA. Statistical analyses showed significantly lower NAA, Cho, and Cr concentrations in the older group (Fig. 1B). Figure 2A demonstrates the neurometabolic connectivity matrices across the cortical regions for all metabolites. Enhanced metabolic connectivity was observed for NAA, Cho, mIns, and Glu, whereas decreases in connectivity were found for mIns and GABA. Averaged regional neurometabolic connectivity within networks is also presented in Fig. 2B. Taken together, mid-aged adults demonstrated reduced NAA and Cho concentrations along with enhanced intra-network metabolic connectivity, whereas higher mIns and GABA levels were accompanied by reduced metabolic connectivity compared to the younger group.
Supporting Image: FIG1_1.png
Supporting Image: FIG2_2.png
 

Conclusions:

Using whole-brain high-resolution MRSI, this study provides novel insights into age-related neurochemical organization of the brain.

Lifespan Development:

Early life, Adolescence, Aging 2

Novel Imaging Acquisition Methods:

MR Spectroscopy 1

Keywords:

ADULTS
MR SPECTROSCOPY
Other - Neurometabolites

1|2Indicates the priority used for review

Abstract Information

By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.

I accept

The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:

I am submitting this abstract as an original work to be reproduced. I am available to be the “source party” in an upcoming team and consent to have this work listed on the OSSIG website. I agree to be contacted by OSSIG regarding the challenge and may share data used in this abstract with another team.

Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Yes

Please indicate which methods were used in your research:

Structural MRI
Other, Please specify  -   MRSI

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Free Surfer

Provide references using APA citation style.

1. Selemon L. D. (2013). A role for synaptic plasticity in the adolescent development of executive function. Translational psychiatry, 3(3), e238.
2. Cleeland, C., Pipingas, A., Scholey, A., & White, D. (2019). Neurochemical changes in the aging brain: A systematic review. Neuroscience and biobehavioral reviews, 98, 306–319.
3. Hermans, L., Leunissen, I., Pauwels, L., Cuypers, K., Peeters, R., Puts, N. A. J., Edden, R. A. E., & Swinnen, S. P. (2018). Brain GABA Levels Are Associated with Inhibitory Control Deficits in Older Adults. The Journal of neuroscience : the official journal of the Society for Neuroscience, 38(36), 7844–7851.
4. Degnan AJ, Ceschin R, Lee V, Schmithorst VJ, Bl ̈ uml S, Panigrahy A (2014) Early metabolic development of posteromedial cortex and thalamus in humans analyzed via in vivo quantitative magnetic resonance spectroscopy. J Comp Neurol 522:3717–3732.
5. Degnan, A. J., Ceschin, R., Lee, V., Schmithorst, V. J., Blüml, S., & Panigrahy, A. (2014). Early metabolic development of posteromedial cortex and thalamus in humans analyzed via in vivo quantitative magnetic resonance spectroscopy. The Journal of comparative neurology, 522(16), 3717–3732.
6. Zhao, Y., Li, Y., Xiong, J., Guo, R., Li, Y., & Liang, Z. P. (2020). Rapid High-Resolution Mapping of Brain Metabolites and Neurotransmitters Using Hybrid FID/SE-J-Resolved Spectroscopic Signals. ISMRM.
7. Liang, Z. P. (2007, April). Spatiotemporal imaging with partially separable functions. In 2007 4th IEEE international symposium on biomedical imaging: from nano to macro (pp. 988-991). IEEE.
8. Lam, F., Ma, C., Clifford, B., Johnson, C. L., & Liang, Z. P. (2016). High‐resolution 1H‐MRSI of the brain using SPICE: data acquisition and image reconstruction. Magnetic resonance in medicine, 76(4), 1059-1070.
9. Ma, C., Lam, F., Johnson, C. L., & Liang, Z. P. (2016). Removal of nuisance signals from limited and sparse 1H MRSI data using a union‐of‐subspaces model. Magnetic resonance in medicine, 75(2), 488-497.
10. Li, Y., Lam, F., Clifford, B., & Liang, Z. P. (2017). A subspace approach to spectral quantification for MR spectroscopic imaging. IEEE Transactions on Biomedical Engineering, 64(10), 2486-2489.

UNESCO Institute of Statistics and World Bank Waiver Form

I attest that I currently live, work, or study in a country on the UNESCO Institute of Statistics and World Bank List of Low and Middle Income Countries list provided.

No