Purpose The circulation of cerebrospinal fluid (CSF) is closely associated with many aspects of brain physiology. When gadolinium(Gd)‐based contrast is administered intravenously, pre‐ and post‐contrast MR signal changes can often be observed in the CSF at certain locations within the intra‐cranial space, mainly due to the lack of a blood‐brain barrier in the dural blood vessels. This study aims to develop and systemically optimize MRI sequences that can detect dynamic signal changes in the CSF after Gd administration with a sub‐millimeter spatial resolution, a temporal resolution of <10 s, and whole brain coverage. Methods Bloch simulations were performed to determine optimal imaging parameters for maximum CSF contrast before and after Gd injection. Simulations were validated with phantom scans. An optimized turbo‐spin‐echo (TSE) sequence was performed on healthy volunteers on 3T and 7T. Results Simulation results agreed well with phantom scans. In human scans, dynamic signal changes after Gd injection in the CSF were detected at several locations where cerebral lymphatic vessels were identified in previous studies. The concentration of Gd in CSF in these regions was estimated to be approximately 0.2 mmol/L. Conclusion Dynamic signal changes induced by the distribution of Gd in the CSF can be detected in healthy human subjects with an optimized TSE sequence. The proposed methodology does not rely on any particular theory on CSF circulation. We expect it to be useful for studies on CSF circulation and cerebral lymphatic vessels in the brain.

Contributors Jun Hua conducted data collection, data analysis and interpretation, drafting of the article, revision of the article, and final approval. Nicholas I.S. Blair conducted the functional MRI data analysis. Adrian Paez contributed to data analysis and revision of the article. Ann Choe contributed to data interpretation and revision of the article. Anita D. Barber contributed to data interpretation and revision of the article. Allison Brandt contributed to the collection and analysis of the clinical data, and revision of the article. Issel Anne L. Lim contributed to data collection. Feng Xu contributed to data interpretation and revision of the article. Vidyulata Kamath contributed to data interpretation and revision of the article. James J. Pekar contributed to study design, data interpretation and revision of the article. Peter C.M. van Zijl contributed to study design, data interpretation, and revision of the article. Christopher A. Ross contributed to study design, data interpretation, and revision of the article. Russell L. Margolis contributed to study design, data analysis and interpretation, drafting of the article, revision of the article, and final approval. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interest Equipment used in the study was manufactured by Philips. Peter C.M. van Zijl receives grant support from Philips, is a paid lecturer for Philips, and is the inventor of technology that is licensed to Philips. This arrangement has been approved by Johns Hopkins in accordance with its conflict of interest policies.

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Olfaction is a fundamental sense that plays a vital role in daily life in humans, and can be altered in neuropsychiatric and neurodegenerative diseases. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) using conventional echo-planar-imaging (EPI) based sequences can be challenging in brain regions important for olfactory processing, such as the olfactory bulb (OB) and orbitofrontal cortex, mainly due to the signal dropout and distortion artifacts caused by large susceptibility effects from the sinonasal cavity and temporal bone. To date, few studies have demonstrated successful fMRI in the OB in humans. T2-prepared (T2prep) BOLD fMRI is an alternative approach developed especially for performing fMRI in regions affected by large susceptibility artifacts. The purpose of this technical study is to evaluate T2prep BOLD fMRI for olfactory functional experiments in humans. Olfactory fMRI scans were performed on 7T in 14 healthy participants. T2prep BOLD showed greater sensitivity than GRE EPI BOLD in the OB, orbitofrontal cortex and the temporal pole. Functional activation was detected using T2prep BOLD in the OB and associated olfactory regions. Habituation effects and a bi-phasic pattern of fMRI signal changes during olfactory stimulation were observed in all regions. Both positively and negatively activated regions were observed during olfactory stimulation. These signal characteristics are generally consistent with literature and showed a good intra-subject reproducibility comparable to previous human BOLD fMRI studies. In conclusion, the methodology demonstrated in this study holds promise for future olfactory fMRI studies in the OB and other brain regions that suffer from large susceptibility artifacts.