Introduction

Developments in quantitative calibrated fMRI have yielded imaging markers of cerebral blood flow (CBF) and cerebral metabolic oxygen consumption (CMRO₂)¹, whereas novel DWI techniques allow for quantitative assessment of microstructural features; the Soma And Neurite Density Imaging (SANDI)² model estimates grey matter (GM) microstructural parameters, including apparent soma radius and density.

Comparing energetic and microstructural data may elucidate neural energy consumption mechanisms. According to the hypothesis that neurons can be modeled as capacitors, larger neurons use more energy because they require more ions to cross the cell membrane to keep cellular homeostasis³. We begin to explore these potential relationships in healthy brain GM.

Methods

Thirty-seven healthy volunteers (age: 32.5±6.5years; 18/19 F/M) underwent calibrated fMRI and DWI. Data were acquired on a Siemens Prisma 3T scanner using a 32-channel receive-only head coil.

Correlation between energy and microstructure metrics was evaluated. Multivariate Linear Regression model parameters, with CBF as dependent variable and SANDI parameters as independent variables, were estimated through variables normalization (z-scoring) and Partial Least Squares Regression (PLSR)⁴. The number of components (N=1) for PLSR model was chosen based on 10-fold cross-validation⁵.

Results and Discussion

Figure 1 shows example maps of CBF, CMRO₂, soma radius and soma density.

Figure 2 reports the positive association across regions between metabolic markers (CBF and CMRO₂) and structural metrics (soma radius and density). The correlation is higher for soma size compared to soma density.

Figure 3 reports the estimated PLSR model parameters. These results suggest that soma size mostly explains CBF variance, supporting the hypothesis of the capacitor model.

References

• Germuska M, Wise RG. Calibrated fMRI for mapping absolute CMRO2: Practicalities and prospects. NeuroImage 2019; 187: 145–153.
• Palombo M, Ianus A, Guerreri M, Nunes D, Alexander DC, Shemesh N, Zhang H. SANDI: A compartment-based model for non-invasive apparent soma and neurite imaging by diffusion MRI. Neuroimage. 2020 Jul 15; 215:116835.
• Quintela-López T, Shiina H, Attwell D. Neuronal energy use and brain evolution. Curr Biol. 2022 Jun 20;32(12): R650-R655.
• Guebel, D.V., Torres, N.V. (2013). Partial Least-Squares Regression (PLSR). In: Dubitzky, W., Wolkenhauer, O., Cho, KH., Yokota, H. (eds) Encyclopedia of Systems Biology. Springer, New York, NY.
• Refaeilzadeh, P., Tang, L., Liu, H. (2009). Cross-Validation. In: LIU, L., ÖZSU, M.T. (eds) Encyclopedia of Database Systems. Springer, Boston, MA.

Acknowledgements

Funded by:

European Union-NextGenerationEU- Italian Ministry of University and Research (MUR), Research National Program (PNR) and Projects of National Relevance (PRIN), Project Code: 2022BERM2F, Project Title: “Mapping Mitochondrial Function and Oxygen Metabolism in the Human Brain with Magnetic Resonance Imaging.” Funding call No. 104 of 02.02.2022, Concession decree No. 1065 of 18.07.2023 adopted by MUR, ERC Panel LS7 “Prevention, Diagnosis and Treatment of Human Diseases”.  CUP: D53D23013410001;

European Union-NextGenerationEU- Italian Ministry of University and Research (MUR), National Plan for Recovery and Resilience (PNRR) and Projects of National Relevance (PRIN), Project Code: P20225AEEE, Project Title: “Hybrid PET-MRI to simultaneously probe brain metabolism and cerebrovascular function in neurodegenerative diseases.” Funding call No. 1409 of 14.09.2022, Concession decree No. 1369 of 01.09.2023 adopted by MUR, ERC Panel LS7 “Prevention, Diagnosis and Treatment of Human Diseases”. CUP: D53D23021480001;

European Union-NextGenerationEU- Italian Ministry of University and Research (MUR), National Plan for Recovery and Resilience (PNRR) and Projects of National Relevance (PRIN), Project Code: P2022ESHT4, Project Title: “Advancing MRI biomarkers of brain tissue microstructure and energetics in Multiple Sclerosis.” Funding call No. 1409 of 14.09.2022, Concession decree No. 1367 of 01.09.2023 adopted by MUR, ERC Panel LS5 “Neuroscience and Disorders of the Nervous System”.  CUP: D53D23019210001;

European Union – NextGenerationEU under the National Plan for Recovery and Resilience (PNRR), Mission 4 Component 2 – M4C2, Investment 1.5 – Call for tender No. 3277 of 30.12.2021 Italian Ministry of Universities Award Number: ECS00000041, Project Title: “VITALITY – Innovation, digitalization and sustainability for the diffused economy in Central Italy,” Concession Decree No. 1057 of 23.06.2022 adopted by the Italian Ministry of University and Research. CUP D73C22000840006;

European Union – NextGenerationEU under the National Plan for Recovery and Resilience (PNRR), Project Title: “MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease,” Concession Decree No. 1553 of 11.10.2022 adopted by the Italian Ministry of University and Research;

EB has received funding from the European Union’s Horizon Europe research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 101066055—acronym HERMES. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Executive Agency (REA). Neither the European Union nor the granting authority can be held responsible for them;

MP is supported by the UKRI Future Leaders Fellowship (MR/T020296/2);

MG is supported by the Wellcome Trust [220575/Z/20/Z].

In collaboration with Siemens Healthineers.