1Department of Neurosciences, Imaging and Clinical Sciences, University “G. D’Annunzio” of Chieti-Pescara, Italy, Chieti, Italy
2Institute for Advanced Biomedical Technologies, University “G. D’Annunzio” of Chieti-Pescara, Italy, Chieti, Italy
The longitudinal relaxation time (T1) of cerebrospinal fluid (CSF) offers insights into tissue-CSF water exchange, which is believed to participate in waste removal from the brain.1 Nonetheless, current MRI protocols for T1 mapping of CSF are limited to two dimensions and low resolution.2,3
This study aimed to develop a high-resolution three-dimensional (3D) protocol for measuring T1 of CSF throughout the entire brain. To achieve this, the 3D-SPACE-FLAIR sequence was optimised to provide 0.9-mm isotropic resolution, two long inversion times (3200 and 7750 ms), and an ultralong echo time (751 ms), yielding two images for inversion-recovery-based T1 mapping without signal contamination from tissue. The total scan duration was 15 minutes.
Whole-brain high-resolution T1 maps of CSF were obtained in five healthy subjects (3 females, 32.2±4.8 years) using the following model to fit inversion recovery data (S):

where c is a constant, and the effective TIs were derived from TI1 and TI1 plus T2 preparation time.
The T1 values of CSF were quantified in two regions of interest: one including the anterior horns of the lateral ventricles (antLV) and the other covering the cortical subarachnoid space (cortSAS). We tested the hypothesis that T1 would be longer in the antLV than in the cortSAS due to higher tissue-CSF exchange rates in the cortSAS.
Results showed T1 values within the expected ranges4 (Figure 1), and regional analysis indicated shortening in areas with increased tissue-CSF water exchange2 (Figure 2). The methodology presented here may help characterise waste removal processes from the whole brain.

Figure 1. T1 map. The T1 values calculated in the global CSF mask are overlaid on the 3D SPACE FLAIR TI2 image shown in Figure 1. The yellow arrows indicate locations where the T1 values are too small to be displayed within the chosen range, and therefore, the underlying 3D SPACE FLAIR TI2 image becomes visible.

Figure 2. Regional T1 values. For each subject and each ROI, the bars represent the mean of T1, whereas the error bars denote the standard deviation of T1. AntLV=anterior horns of the lateral ventricles. cortSAS=cortical subarachnoid space.
References
- Agarwal N, Lewis LD, Hirschler L, et al. Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 “ ISMRM Imaging Neurofluids Study group” Workshop in Rome. Magnetic Resonance Imaging. 2024;59(2):431-449. doi:10.1002/jmri.28759
- Jiang D, Gou Y, Wei Z, Hou X, Yedavalli V, Lu H. Quantification of T 1 and T 2 of subarachnoid CSF : Implications for water exchange between CSF and brain tissues. Magnetic Resonance in Med. 2023;90(6):2411-2419. doi:10.1002/mrm.29829
- Zaharchuk G, Martin AJ, Rosenthal G, Manley GT, Dillon WP. Measurement of cerebrospinal fluid oxygen partial pressure in humans using MRI. Magnetic Resonance in Medicine. 2005;54(1):113-121. doi:10.1002/mrm.20546
- Bojorquez JZ, Bricq S, Acquitter C, Brunotte F, Walker PM, Lalande A. What are normal relaxation times of tissues at 3 T? Magnetic Resonance Imaging. 2017;35:69-80. doi:10.1016/j.mri.2016.08.021
Acknowledgements
This project 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.
Funded in part by the European Union – NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem grant ECS00000041 – VITALITY – CUP D73C22000840006.
European Union-NextGenerationEU – Italian Ministry of University and Research, Research Projects of National Relevance (PRIN), Project Code: 2022BERM2F, Project Title: “Mapping Mitochondrial Function and Oxygen Metabolism in the Human Brain with Magnetic Resonance Imaging.” Concession decree No. 1065 of 18. 07.2023 adopted by the Italian Ministry of University and Research, ERC Sector LS7 “Prevention, Diagnosis and Treatment of Human Diseases.”
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