Respiratory cerebrospinal fluid flow is driven by the thoracic and lumbar spinal pressures.

KEY POINTS: Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system. During inspiration increased venous return from the cranium is believed to draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration. We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures. These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory-related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections. ABSTRACT: It is accepted that during inspiration, cerebrospinal fluid (CSF) flows rostrally to compensate for decreased cranial blood volume, caused by venous drainage due to negative intrathoracic pressure. However, this mechanism does not explain observations of caudal CSF displacement during inspiration. Determining the drivers of respiratory CSF flow is crucial for understanding the pathophysiology of CSF flow disorders. To quantify the influence of respiration on CSF flow, real-time phase-contrast magnetic resonance imaging (MRI) was used to record CSF and blood flow, while healthy subjects (5:5 M:F, 25-50 years) performed either a brief expiratory or inspiratory effort between breaths. Transverse images were taken perpendicular to the spinal canal in the middle of the C3 and L2 vertebrae. The same manoeuvres were then performed after a nasogastric pressure catheter was used to measure the intrathoracic and abdominal pressures. During expiratory-type manoeuvres that elevated abdominal and intrathoracic pressures, epidural blood flow into the spinal canal increased and CSF was displaced rostrally. With inspiratory manoeuvres, the negative intrathoracic pressure drew venous blood from C3 and L2 towards the thoracic spinal canal, and cervical CSF was displaced both rostrally and caudally, despite the increased venous drainage. Regression analysis showed that rostral displacement of CSF at both C3 (adjusted R2  = 0.53; P < 0.001) and L2 (adjusted R2  = 0.38; P < 0.001) were associated with the abdominal pressure. However, with low abdominal pressure and comparably negative intrathoracic pressure, cervical CSF flowed caudally. These findings suggest that changes in both the cranial and spinal pressures need to be considered to understand respiratory CSF flow.

19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:343-354.

In vivo regional ventilation mapping using fluorinated gas MRI with an x-centric FGRE method.

PURPOSE: Inert fluorinated gas lung MRI is a new and promising alternative to hyperpolarized gas lung MRI; it is less expensive and does not require expensive isotopes/polarizers. The thermally polarized nature of signal obtained from fluorinated gases makes it relatively easy to use for dynamic lung imaging and for obtaining lung ventilation maps. In this study, we propose that the sensitivity and resolution of fluorine-19 (19F) in vivo images can be improved using the x-centric pulse sequence, thereby achieving a short echo time/pulse repetition time. This study is a transitional step for converting to more sustainable gases for lung imaging. METHODS: A 19F-resolution phantom was used to validate the efficiency of performing the x-centric pulse sequence on a clinical scanner. Ventilation maps were obtained in the lungs of five normal rats with a washout approach (adapted from Xe-enhanced computed tomography [Xe-CT] regional ventilation mapping), using mixtures of either sulfur hexafluoride/oxygen or perfluoropropane/oxygen and a two-breath x-centric method. RESULTS: Fractional ventilation (r) values obtained in this study (0.35-0.46 interval) were in good agreement with previously published values for 3He/129Xe. Calculated r gradients agreed well with published gradients obtained in rats with Xe-CT measurements. CONCLUSIONS: These results suggest that fluorinated gases can be reliably used in vivo in dynamic lung studies as an alternative to 3He/129Xe.

Inert fluorinated gas MRI: a new pulmonary imaging modality.

Fluorine-19 ((19)F) MRI of the lungs using inhaled inert fluorinated gases can potentially provide high quality images of the lungs that are similar in quality to those from hyperpolarized (HP) noble gas MRI. Inert fluorinated gases have the advantages of being nontoxic, abundant, and inexpensive compared with HP gases. Due to the high gyromagnetic ratio of (19)F, there is sufficient thermally polarized signal for imaging, and averaging within a single breath-hold is possible due to short longitudinal relaxation times. Therefore, the gases do not need to be hyperpolarized prior to their use in MRI. This eliminates the need for an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the lungs has been previously demonstrated in animals, and more recently in healthy volunteers and patients with lung diseases. The ongoing improvements in image quality demonstrate the potential of (19)F MRI for visualizing the distribution of ventilation in human lungs and detecting functional biomarkers. In this brief review, the development of inert fluorinated gas MRI, current progress, and future prospects are discussed. The current state of HP noble gas MRI is also briefly discussed in order to provide context to the development of this new imaging modality. Overall, this may be a viable clinical imaging modality that can provide useful information for the diagnosis and management of chronic respiratory diseases.

Pulmonary ultrashort echo time 19F MR imaging with inhaled fluorinated gas mixtures in healthy volunteers: feasibility.

PURPOSE: To perform static breath-hold fluorine 19 ((19)F) three-dimensional (3D) ultrashort echo time (UTE) magnetic resonance (MR) imaging of the lungs in healthy volunteers by using a mixture of 79% perfluoropropane (PFP) and 21% O2. MATERIALS AND METHODS: This study protocol was approved by the local research ethics board and by Health Canada. All volunteers provided written informed consent. Ten healthy volunteers underwent MR imaging at 3.0 T. Fluorine 19 3D UTE MR images were acquired during a 15-second breath hold according to one of two breathing protocols: protocol A, a 1-L inhalation of a mixture of 79% PFP and 21% O2, and protocol B, continuous breathing from a 5-L bag of a mixture of 79% PFP and 21% O2 followed by a 1-L inhalation of the same PFP-O2 mixture from a separate bag and a subsequent breath hold. The signal-to-noise ratio (SNR) was measured in the three most central image sections and was compared between breathing protocols by using an unpaired t test. RESULTS: Overall, the SNR was significantly greater for breathing protocol B (continuous breathing) than for breathing protocol A (single breath) (P = .018). The mean SNRs were 18 ± 6 (standard deviation) and 32 ± 6 for images acquired by using breathing protocols A and B, respectively. Breathing protocol B improves SNR by "washing out" the air from the lungs and increasing the PFP concentration prior to (19)F imaging. CONCLUSION: This study demonstrates the feasibility of (19)F 3D UTE static breath-hold MR imaging of human lungs with inert fluorinated gases.