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Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI.

ABSTRACT: Recent studies have suggested the glymphatic system as a key mechanism of waste removal in the brain. Dynamic contrast-enhanced MRI (DCE-MRI) using intracisternally administered contrast agents is a promising tool for assessing glymphatic function in the whole brain. In this study, we evaluated the transport kinetics and distribution of three MRI contrast agents with vastly different molecular sizes in mice. Our results demonstrate that oxygen-17 enriched water (H₂¹⁷O), which has direct access to parenchymal tissues via aquaporin-4 water channels, exhibited significantly faster and more extensive transport compared to the two gadolinium-based contrast agents (Gd-DTPA and GadoSpin). Time-lagged correlation and clustering analyses also revealed different transport pathways for Gd-DTPA and H₂¹⁷O. Furthermore, there were significant differences in transport kinetics of the three contrast agents to the lateral ventricles, reflecting the differences in forces that drive solute transport in the brain. These findings suggest the size-dependent transport pathways and kinetics of intracisternally administered contrast agents and the potential of DCE-MRI for assessing multiple aspects of solute transport in the glymphatic system.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC10449788 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI.

Zhu Yuran Y Wang Guanhua G Kolluru Chaitanya C Gu Yuning Y Gao Huiyun H Zhang Jing J Wang Yunmei Y Wilson David L DL Zhu Xiaofeng X Flask Chris A CA Yu Xin X

Scientific reports 20230824 1

Recent studies have suggested the glymphatic system as a key mechanism of waste removal in the brain. Dynamic contrast-enhanced MRI (DCE-MRI) using intracisternally administered contrast agents is a promising tool for assessing glymphatic function in the whole brain. In this study, we evaluated the transport kinetics and distribution of three MRI contrast agents with vastly different molecular sizes in mice. Our results demonstrate that oxygen-17 enriched water (H<sub>2</sub><sup>17</sup>O), whi ...[more]

PMID: 37620371

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Project description:BackgroundCervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype.MethodsThirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration.ResultsThe frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one.ConclusionsThe spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape.

Dataset Information

Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI.

Publications

Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI.

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