Lydiane Hirschler¹, Bobby A Runderkamp², Susanne J van Veluw^1,3, Matthan WA Caan⁴, and Matthias JP van Osch^1
1Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, ³Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ⁴Biomedical Engineering & Physics, Amsterdam University Medical Center, Amsterdam, Netherlands

Although research into brain waste clearance has recently gained increasing attention, the driving force(s) as well as the physiological processes involved still remain strongly debated. Here, we assess the influence of the cardiac cycle and of respiration on the mobility of cerebrospinal fluid (CSF), thought to be an important waste carrier. We found that the cardiac cycle was inducing higher CSF-mobility changes than respiration.

Liu Pan^1,2, Sidy Fall¹, Serge Metanbou³, and Olivier Baledent^1,2
1CHIMERE UR 7516, Jules Verne University, Amiens, France, ²Medical Image Processing Department, Jules Verne University Hospital, Amiens, France, ³Department of Radiology, Jules Verne University Hospital, Amiens, France

Real-time phase contrast MRI has been applied to investigate cerebral arterial blood flow (CABF) during normal breathing of healthy volunteers. We developed a novel time-domain analysis method to quantify the effect of normal breathing on several parameters of CABF. We found the existence of a delay between the recorded respiratory signal from the belt sensor and the breathing frequency component presents in the reconstructed arterial blood flows. During the expiratory, the mean flow rate of CABF increased by 4.4±1.7%, stroke volume of CABF increased by 9.8±3.1% and the duration of the cardiac period of CABF increased by 8.1±3%.

Qiuting Wen¹, Yunjie Tong², Xiaopeng Zhou³, Chang Yueh Ho¹, and Yu-Chien Wu^1
1Indiana University, School of Medicine, Indianapolis, IN, United States, ²Weldon School of Biomedical Engineering Department, Purdue University, West Lafayette, IN, United States, ³School of Health Sciences, Purdue University, West Lafayette, IN, United States

We introduce an MRI technique named CARDI, for in-vivo assessment of pulsatile fluid dynamics in the surface paravascular spaces of the pial arteries. A pair of pulsed gradient spin echo was used to detect the slow flow of CSF while suppressing the fast flow of adjacent arterial blood. Waveform of CSF over a cardiac cycle is revealed. The shape of the CSF waveforms closely resembles the pressure waveforms of the artery wall, suggesting that CSF dynamics is tightly related to artery wall mechanics. The comparison of CSF waveforms in an aging group revealed a significant age-dependency of the CSF waveforms. 

Johannes Töger¹, Mads Andersen^2,3, Olle Haglund⁴, Tekla Kylkilahti^5,6, Iben Lundgaard^5,6, and Karin Markenroth Bloch^3
1Department of Clinical Sciences, Diagnostic Radiology, Skane University Hospital Lund, Lund University, Lund, Sweden, ²Philips Healthcare, Copenhagen, Denmark, ³Lund University Bioimaging Center, Lund University, Lund, Sweden, ⁴Department of Medical Radiation Physics, Lund University, Lund, Sweden, ⁵Department of Experimental Medical Science, Lund University, Lund, Sweden, ⁶Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden

Methods to quantify CSF flow dynamics are important to study the physiology of intracranial pressure variations. Respiration influences the CSF flow, making real-time acquisitions necessary. This work investigates a high-resolution radial real-time flow sequence with golden angle acquisition and compressed sensing reconstruction at 7T for flow quantification of the CSF flow in the aqueduct. Phantom data shows that the proposed method accurately quantifies the slower aqueduct CSF flow oscillations caused by respiration, but underestimates faster cardiac oscillations. In vivo data shows good repeatability and an association between respiratory condition and net CSF flow.

Yuran Zhu¹, Yuning Gu¹, Kihwan Kim¹, Chaitanya Kolluru¹, Huiyun Gao², Yunmei Wang^2,3, David L. Wilson^1,4,5, Chris A. Flask^1,4,6,7,8, and Xin Yu^1,4,9
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States, ³Department of Medicine, Case Western Reserve University, Cleveland, OH, United States, ⁴Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁵Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States, ⁶Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States, ⁷Imaging Research Core, Case Western Reserve University, Cleveland, OH, United States, ⁸Cancer Imaging Program, Case Western Reserve University, Cleveland, OH, United States, ⁹Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

This study compared the transport of three MRI contrast agents with different molecular sizes (Gd-DTPA, GadoSpin, and H₂¹⁷O) in the mouse glymphatic system with dynamic contrast-enhanced MRI. Dynamic signal changes in the whole-brain and selected regions of interest (ROI) were analyzed. The results showed drastically different kinetics of the three tracers, indicating differences in glymphatic transport routes and rates. The current work lays the foundation for future studies employing genetically manipulated mouse models for mechanistic understanding of the regulation of glymphatic function in normal and diseased conditions.

Anna Li¹, Chen Lin^1,2, Hongshuai Liu³, Yuguo Li^1,4, Wenzhen Duan³, and Jiadi Xu^1,4
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ²Department of Electronic Science, Xiamen University, Xiamen, China, ³Division of Neurobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Our understanding of the CSF exchange with surrounding tissues and its correlation with brain function is limited. We presented a non-invasive magnetization transfer indirect spin labeling (MISL) MRI method to quantify the water exchange between cerebrospinal fluid (CSF) and surrounding tissues in the brain by making use of the significantly different protein concentrations between CSF and other tissues. Water in the surrounding tissue is directly labeled by magnetization transfer from the abundant macromolecule pool. The reduction in the CSF signal corresponds to the water traveled to CSF, which is strongly age-dependent and weakly AQP4-dependent.  

Merel M. van der Thiel^1,2, Nathalie A. Roos^1,3, Gerhard S. Drenthen^1,2, Paulien H.M. Voorter^1,2, Thorsten Feiweier⁴, Inez H.G.B. Ramakers^2,5, Walter H. Backes^1,2,6, and Jacobus F.A. Jansen^1,2,7
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²School for Mental Health & Neuroscience, Maastricht University, Maastricht, Netherlands, ³Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, ⁴Siemens Healthcare, Erlangen, Germany, ⁵Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, Netherlands, ⁶School for Cardiovascular Disease, Maastricht University, Maastricht, Netherlands, ⁷Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Between the parenchymal and microvascular diffusion components, a third, intermediate component can be derived with cerebral IVIM. Its fraction (f_int) seems a promising biomarker for altered cerebral clearance function. f_int has been suggested to both be driven by fluid diffusivity within enlarged perivascular spaces (ePVS) and interstitial fluid between parenchymal cells. Using 7T MRI, this study determined a higher f_int within the ePVS (through segmented masks) compared to surrounding non-ePVS tissue. Thereby, this study illustrates the contribution of ePVS fluid diffusivity to f_int and highlights the ability to specifically assess ePVS fluid diffusion using a non-invasive MRI method.

Anders Wåhlin^1,2,3, Anders Garpebring³, Klara Mogensen³, Tomas Vikner³, Cecilia Björnfot³, Sara Qvarlander³, Jan Malm⁴, and Anders Eklund^2,3
1Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden, ²Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden, ³Department of Radiation Sciences, Umeå University, Umeå, Sweden, ⁴Department of Clinical Science, Umeå University, Umeå, Sweden

The pathways of brain molecular clearance and potential glymphatic efflux to extracerebral cerebrospinal fluid is a matter of intense research. We investigated possible contrast enrichment in cerebrospinal fluid of the subarachnoid space following intravenous contrast injection. This approach utilizes a subtle but widespread contrast leakage across the blood-brain barrier that potentially enables the investigation of glymphatic function. Using T1-mapping as well as dynamic scanning during contrast infusion, we present data consistent with a model where molecules cleared from the brain enter subarachnoid space cerebrospinal fluid. This approach could be a clinically feasible alternative for investigating brain molecular clearance in humans.