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Vadim Malis¹, Won Bae^1,2, Asako Yamamoto³, Linda McEvoy¹, Marin McDonald¹, and Mitsue Miyazaki^1
1Radiology, University of California, San Diego, La Jolla, CA, United States, ²VA San Diego Healthcare System, San Diego, CA, United States, ³Radiology, Teikyo University, Tokyo, Japan

Keywords: Neurofluids, Aging, cerebrospinal fluid (CSF), intrinsic CSF outflow, egress pathways

Parasagittal dura (PSD) along the superior sagittal sinus (SSS) can be visualized using FLAIR and 3D SSFSE without gadolinium-contrast administration. Visualization of intrinsic CSF outflow from the PSD to the SSS can be achieved in human brains using spin-labeling MRI at clinical 3-T MRI. The spin-labeling MRI shows intrinsically tagged CSF outflow from the upper PSD and lower PSD to SSS. The quantitative intrinsic CSF outflow metrics indicate an age-related decline of the intrinsic CSF outflow at the SSS in human brains.

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Qiuting Wen¹, Adam Wright^1,2, Yunjie Tong², Yi Zhao¹, Shannon L. Risacher¹, Andrew J. Saykin¹, Yu-Chien Wu¹, Kalen Riley¹, and Kaustubh Limaye^1
1Indiana University, School of Medicine, Indianapolis, IN, United States, ²Weldon School of Biomedical Engineering Department, Purdue University, West Lafayette, IN, United States

Keywords: Neurofluids, Aging

We recently developped a novel technique, dynamic diffusion-weighted imaging (dDWI), for measuring paravascular cerebrospinal fluid (pCSF) dynamics.  In this work, we evaluated the time shifts between the pulsation-driven pCSF waves (measured by dDWI) and finger pulse waves (measured by scanner’s built-in finger pulse oximeter) to calculate brain-finger pulse wave travel time.  Our preliminary results of an aging cohort support that the dDWI-derived brain-finger TimeDelay can be a surrogate for arterial stiffness.  This method can be used as an add-on analysis to the recently developed dDWI framework to offer information about the participant’s vascular conditions. 

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Liangdong Zhou¹, Yi Li¹, Gloria C Chiang¹, Elizabeth Sweeney², Xiuyuan H Wang¹, Susan Gauthier¹, Yi Wang¹, Amy Kuceyeski¹, Mony de Leon¹, and Thanh Nguyen^1
1Weill Cornell Medicine, New York, NY, United States, ²University of Pennsylvania, Philadelphia, PA, United States

Keywords: Neurofluids, Aging

Water homeostasis in brain involves the fluid dynamic through the intracellular fluid, extracellular fluid and CSF, and it’s important to help maintaining the brain function. The change of water compartments with aging may reflect the physiology and pathophysiology of the brain.  We mapped the brain CSF water fraction, myelin water fraction and intro-extracellular water fraction using an MR FAST-T2 relaxometry approach. We found the brain CSF water quadratically increases with normal aging. Myelin water increases before the 50s and then decrease in adults. Intro-extracellular water decreases in the adult lifespan. This results are impactful for understanding the glymphatic clearance mechanism.

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Alexander K Song^1,2, Kilian Hett¹, Jarrod J. Eisma¹, Colin D. Mcknight³, Jason Elenberger¹, Adam J. Stark¹, Hakmook Kang^4,5, Ciaran M. Considine¹, Manus J. Donahue¹, and Daniel O. Claassen^1
1Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ²Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, United States, ³Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ⁴Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, United States

Keywords: Neurofluids, Alzheimer's Disease

A pathological hallmark of Alzheimer’s disease (AD) is the elevated aggregation of protein amyloid-β (Aβ) in the cerebrum. Recent studies have suggested a role for the parasagittal dural (PSD) space in cerebrospinal fluid (CSF) egress and associated protein clearance. A fully connected neural network was used to generate PSD segmentation masks from 3D T₂-weighted turbo-spin-echo data to assess the relationship between PSD space volume and Aβ burden estimated by ¹¹C-Pittsburgh Compound B in AD participants. PSD space hypertrophy was significantly associated with elevated Aβ levels and was localized to the frontal and parietal subsegments of the PSD.

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Yoshitaka Bito^1,2, Hisaaki Ochi^1,2, Ryuji Shirase¹, Wataru Yokohama¹, Kuniaki Harada², and Kohsuke Kudo^2
1FUJIFILM Healthcare Corporation, Tokyo, Japan, ²Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Keywords: Neurofluids, Diffusion/other diffusion imaging techniques

Low b-value DTI (Low-b DTI) has been recently proposed for investigating the CSF motion. Here, an analysis technique using the Low-b DTI was proposed for resolving intravoxel incoherent motion into ordered (linear) and disordered (random) motions of the CSF. A normal-subject study demonstrated that the proposed technique can differentiate characteristics of the complex CSF motion in typical ROIs. The proposed technique can be useful in investigating the dynamics of neurofluids.

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Sang-Young Kim¹, Eunju Kim¹, Jinwoo Hwang¹, Joo Hyun Kim¹, and Chae Jung Park^2
1Health Systems, Philips Healthcare, Seoul, Korea, Republic of, ²Department of Radiology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea, Republic of

Keywords: Neurofluids, Diffusion Tensor Imaging

Non-invasive measure of glymphatic function or flow in vivo has gained a great attention from neuroscience research community. Diffusion tensor imaging (DTI) can provide a mean that measures the diffusivity along perivascular space (ALPS). However, conventional DTI captures diffusion indices from both tissue and free water compartments due to partial volume effects, which may raise a concern about validity of DTI-ALPS index for glymphatic function. In this work, we present a novel method that can extract extracellular diffusivity (i.e., eALPS) using free water eliminated DTI and investigate the relationship between eALPS and structural abnormalities in brain.   

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Yuhan Bian^1,2,3, Ning Wang⁴, Di Cao^1,2,3, Yuanqi Sun^1,2,3, Chunming Gu^1,2,3, Yinghao Li^1,2,3, Jiangyang Zhang⁵, Peter C.M. Van Zijl^1,2, Xiaobo Mao⁴, and Jun Hua^1,2
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²Neurosection, Division of MRI Research, Department of Radiology, Johns Hopkins, Baltimore, MD, United States, ³Department of Biomedical Engineering, Johns Hopkins, Baltimore, MD, United States, ⁴Department of Neurology, Johns Hopkins, Baltimore, MD, United States, ⁵Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States

Keywords: Neurofluids, Alzheimer's Disease

The choroid plexus (CP) is a gateway for the exchange of various metabolites between the microvasculature and brain. Impairment of CP has been reported in various diseases. Recently, dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was developed to measure Gd-induced signal changes in the CSF. Here, cDSC MRI was performed with Intraperitoneal Gd-injection in a tauopathy mouse model to examine CP permeability. The maximal Gd-induced signal change was greater in the ventricles in tau mice than WT mice, indicating an increase of Gd leakage from the microvasculature into the ventricles through the CP.

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Yuichi Morita^1,2, Koji Kamagata¹, Kaito Takabayashi¹, Christina Andica^1,3, Junko Kikuta¹, Shohei Fujita^1,2, Hiroki Tabata⁴, Hitoshi Naito⁵, Yuki Someya^4,6, Hideyoshi Kaga⁵, Toshiaki Akashi¹, Akihiko Wada¹, Yoshifumi Tamura^4,5, Ryuzo Kawamori^4,5, Hirotaka Watada^4,5, Toshiaki Taoka⁷, Shinji Naganawa⁸, Osamu Abe², and Shigeki Aoki^1
1Department of Radiology, Graduate School of Medicine, Juntendo university, Tokyo, Japan, ²Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, ³Faculty of Health Data Science, Juntendo University, Chiba, Japan, ⁴Sportology Center, Graduate School of Medicine, Juntendo university, Tokyo, Japan, ⁵Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo university, Tokyo, Japan, ⁶Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan, ⁷Department of Innovative Biomedical Visualization, Graduate School of Medicine, Nagoya University, Aichi, Japan, ⁸Department of Radiology, Graduate School of Medicine, Nagoya University, Aichi, Japan

Keywords: Neurofluids, Diffusion Tensor Imaging, Glymphatic system, DTI-ALPS

Excessive alcohol intake seriously damages the brain. Previous animal studies reported that the glymphatic system, which is a brain waste clearance system via the cerebral spinal fluid, is affected by chronic high alcohol consumption. Glymphatic dysfunction is related to cognitive impairment. The changes of diffusivity along the perivascular space (ALPS) indices associated with heavy, moderate, and no‑alcohol intake and executive function with or without aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was evaluated. The present study revealed the glymphatic function and executive function decline in heavy drinkers. Furthermore, ALDH2 rs671 variants may increase vulnerability to alcohol-induced glymphatic dysfunction.

Wang Junying¹, Pylypenko Dmytro ², and Shi Hao^1
1Department of Radiology,, The First Affiliated Hospital of Shandong First Medical University, Jinan, China, ²GE Healthcare,, Beijing, China

Keywords: Neurofluids, Diffusion/other diffusion imaging techniques, Arachnoid Cyst;Mega Cisterna Magna

The differences between TAC, MCM and CMAC were measured respectively. For TAC and CMAC groups, both ADC and eADC value showed no statistical difference. There was a statistically significant difference in eADC between TAC and MCM, but no significant difference in ADC.

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Gerhard Drenthen¹, Paulien HM Voorter¹, Maud van Dinther², Julie Staals², Robert J van Oostenbrugge², Walter H Backes¹, and Jacobus FA Jansen^1
1Department of Radiology & Nuclear Medicine, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, Netherlands, ²Department of Neurology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, Netherlands

Keywords: Neurofluids, Relaxometry, Interstitial fluid

Local increases of interstitial fluid (ISF) predates axonal damage in white matter hyperintensities (WMH). However, it is challenging to disentangle these processes on T2w-MRI. By using multi-b-value diffusion and multi-echo T2-relaxometry imaging, we aimed to quantify markers of ISF volume and mobility in patients with vascular cognitive impairment (VCI) and healthy controls (HC). A trend for a higher mobility and volume of ISF was found in VCI patients compared to HC. Moreover, in VCI, elevated mobility of ISF was already present in perilesional tissue compared to normal-appearing white matter, suggesting that it might be an early marker of WMH development.

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Hiroyuki Tatekawa¹, Shu Matsushita¹, and Yukio Miki^1
1Department of Diagnostic and Interventional Radiology, Osaka Metropolitan University, Osaka, Japan

Keywords: Neurofluids, Diffusion Tensor Imaging, ALPS index; glymphatic system;

Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is expected to reflect the glymphatic function of the brain, however, head rotation may reduce reliability. This study evaluated whether a reorientation technique, which registers image and vector information of DTI data, improves the reproducibility of the calculation of the ALPS index. A total of 234 cognitively normal subjects were selected from the OASIS-3 dataset. In the evaluation of the intra- and inter-reliability, the reorientation technique enabled to show good to excellent reproducibility (intraclass correlation coefficients > 0.85) in calculating ALPS index even when head rotation existed.

Yawen Xiao¹, Shiqi Chen¹, Zhaotao Zhang¹, Jiankun Dai², Yifei Gui¹, and Xinlan Xiao^1
1Department of Radiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China, ²GE Healthcare, MR Research China, Beijing, China

Keywords: Neurofluids, Velocity & Flow

Foramen magnum decompression (FMD) is the most used surgical treatment for Chiari malformation type I patients. However, 25～33% of them have persistent  symptoms after surgery. This study aimed at investigating the possibility to predict the FMD outcome by using cerebral fluid (CSF) hydrodynamics and 4th ventricle outlet morphology obtained from magnetic resonance imaging. 27 patients were included and 17 of them had improved outcomes after FMD. Our results showed the peak diastolic velocity of CSF in aqueduct and the width of 4th ventricle outlet were associated with the FMD outcome and combining them can improve the prediction performance.

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Leonardo A. Rivera-Rivera¹, Grant S. Roberts¹, Anthony Peret¹, Sterling C. Johnson¹, Oliver Wieben¹, Laura Eisenmenger¹, and Kevin M. Johnson^1
1University of Wisconsin, Madison, Madison, WI, United States

Keywords: Neurofluids, Velocity & Flow, Aging

In this study, we investigated diurnal changes in cerebral hemodynamics from 4D-Flow in a large population of cognitively healthy older adults and in a younger group of healthy volunteers. To separate physiological and technical variability of 4D-Flow measures, volunteers were scanned at 7am, 4pm, and 10pm on the same day three times for each timepoint. Data supports strong cerebral blood flow fluctuations of physiological origin that are much higher than the technical variability.

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Adrian RUIZ-CHIAPELLO¹, Muriel MESCAM¹, Nathalie VAYSSIERE¹, Isabelle BERRY¹, and Florence REMY-EL BOUSTANI^1
1CerCo, UMR 5549, CNRS/Toulouse 3 University, Toulouse, France

Keywords: Neurofluids, Velocity & Flow, Cerebrospinal fluid

Papers have shown a correlation between CSF flow in the fourth ventricle (V4) and EEG, and also that the low-frequency components (LFC) of EEG were positively correlated with glymphatic system (GS) activity. Analysis of the LFC of CSF flow could be a biomarker of GS degradation. We assessed 6 individuals by using an EPI phase contrast sequence to quantify the time evolution of CSF velocity in V4, and a fMRI sequence with which we exploited the inflow effect phenomenon. EPI-PC highlights the frequencies of physiological phenomena involved in CSF motion, and allows us to quantify LFC, indicative of GS efficiency.

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Ying-Chia Lin¹, Xingye Chen¹, Simon Henin^2,3, Nahbila-Malikha Kumbella¹, Liz Aguilera¹, Zena Rockowitz³, Ashley Clayton³, James Babb¹, Yulin Ge¹, Arjun Masurkar^2,3, Anli Liu^2,3, Yvonne W. Lui^1,4, Fernando E. Boada^1,5, and Yongxian Qian^1
1Department of Radiology, NYU Grossman School of Medicine, New York, NY, United States, ²Department of Neurology, NYU Grossman School of Medicine, New York, NY, United States, ³Department of Neurology, NYU Langone Health, New York, NY, United States, ⁴Department of Radiology, NYU Langone Health, New York, NY, United States, ⁵Department of Radiology, Stanford University, Stanford, CA, United States

Keywords: Neurofluids, Velocity & Flow, Sodium MRI, CSF flow, Sleep

Cerebrospinal fluid (CSF) flow plays a key role in clearance of waste proteins from the brain. Current proton (¹H) MRI is limited to measurement of CSF flow in specific regions such as the aqueduct, due to the lack of capability distinguishing CSF from water.  Sodium (²³Na) MRI is uniquely sensitive to CSF, instead of water, and has the potential to measure CSF flow in entire brain. Here, we use a recently-developed dynamic sodium MRI to measure CSF flow velocity in the brain and to understand how it changes with sleep state monitored by MRI-compatible EEG.

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Xingye Chen¹, Ying-Chia Lin¹, Simon Henin^2,3, Nahbila-Malikha Kumbella¹, Liz Aguilera¹, Zena Rockowitz³, Ashley Clayton³, Shichun Chen⁴, Weiying Dai⁴, James Babb¹, Yulin Ge¹, Arjun Masurkar^2,3, Yvonne W. Lui^1,5, Fernando E. Boada^1,6, Anli Liu^2,3, and Yongxian Qian^1
1Radiology, NYU Grossman School of Medicine, New York, NY, United States, ²Neurology, NYU Grossman School of Medicine, New York, NY, United States, ³Neurology, NYU Langone Health, New York, NY, United States, ⁴Department of Computer Science, State University of New York at Binghamton, Binghamton, NY, United States, ⁵Radiology, NYU Langone Health, New York, NY, United States, ⁶Radiology, Stanford University, Stanford, CA, United States

Keywords: Neurofluids, Velocity & Flow, MRI-compatible EEG, Sodium MRI, Sleep, Extracellular Space

Sleep is reported in mince studies to increase extracellular space and improve CSF clearance of amyloid beta proteins from the animal brains. However, it is unclear whether sleep also benefits humans. This study used simultaneous MRI-compatible EEG to monitor sleep stage of human study subjects and used sodium MRI to quantify extracellular volume fraction. We seek to find the association between sleep stage and extracellular volume change in the human brain.

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Jun-Hee Kim¹ and Sung-Hong Park^1
1Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of

Keywords: Neurofluids, Traumatic brain injury

A recently-proposed method of simultaneous CSF pulsation and BOLD activity imaging was applied to the TBI-fMRI dataset. The CSF pulsation was significantly lower in the TBI group compared to that of healthy control group. The CSF pulsation decreased significantly in the first 6 months after TBI and then no significant changes in the later stage, which was consistent with previous studies, where CSF pulsation from TBI patients was lower than that of control subjects and starts to slowly recover thereafter. This study can be expanded to post-TBI fMRI datasets in general to examine functional activity and CSF pulsation simultaneously.

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Yuran Zhu¹, Guanhua Wang², Yuning Gu¹, Huiyun Gao^3,4, Jing Zhang⁵, Yunmei Wang^3,4, Xiaofeng Zhu⁵, Chris A. Flask^1,6,7, and Xin Yu^1,6,8
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States, ³Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States, ⁴Department of Medicine, Case Western Reserve University, Cleveland, OH, United States, ⁵Department of Biostatistics, Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States, ⁶Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁷Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States, ⁸Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

Keywords: Neurofluids, Contrast Agent, Glymphatics

This study investigated the impact of molecular size on transport kinetics and distribution of intracisternal tracers in mouse brain. Three MRI contrast agents with different molecular sizes were administered via cisterna magna. Their transport in the whole brain was observed by dynamic contrast-enhanced MRI for 2 hours. Our results show that the transport of ¹⁷O-water (H₂¹⁷O) was significantly faster and more extensive than the two gadolinium-based tracers (Gd-DTPA and GadoSpin). Time-lagged correlation analysis and clustering analysis also showed different cluster patterns between Gd-DTPA and H₂¹⁷O. These observations suggest the size-dependent differences in forces that drive tracer transport in the brain.

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Haribalan Kumar^1,2,3, Haylea Rodgers^3,4, Jet Wright^3,4, Ben Bristow^3,4, Paul Condron^3,5, Taylor Emsden^3,5, Davidson Taylor^3,6, Samantha Holdsworth^3,5, Soroush Safaei², Gonzalo Maso Talou², Josh McGeown³, Ed Maunder⁷, and Eryn Kwon^2,3,5
1GE Healthcare, Gisborne, New Zealand, ²Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand, ³Mātai Medical Research Institute, Gisborne, New Zealand, ⁴University of Otago, Dunedin, New Zealand, ⁵Faculty of Medical and Health Sciences & Centre for Brain Research, University of Auckland, Auckland, New Zealand, ⁶Ngai Tāmanuhiri, Rongowhakaata, Ngāti Porou, Tūranganui-a-Kiwa, Tūranganui-a-Kiwa, Tairāwhiti, New Zealand, ⁷Sports Performance Research Institute New Zealand, Auckland University of Technology, Auckland, New Zealand

Keywords: Neurofluids, Neuroscience, Brain motion, image analysis

Cardiac pulsatility is a key driver of brain pulsatility. However, changes in brain pulsatility in response to changes in heart rate have been sparsely studied. Using a combination of amplified MRI and phase-contrast MRI, brain parenchyma motion, blood flow, and CSF flow were measured and assessed during rhythmic hand-grip exercise to help understand the role of heart rate on brain physiology. This approach opens opportunities for probing the role of heart rate, brain fluid, and motion flow in various pathologies that affect the brain.

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Maho Kitagawa¹, Daisuke Sawamura², Yuta Urushibata³, Hiroyuki Hamaguchi¹, Philip Kyeremeh Jnr Oppong¹, Daiki Sakamoto¹, and Khin Khin Tha^1,4
1Laboratory for Biomarker Imaging Science, Hokkaido University Graduate School of Biomedical Science and Engineering, Sapporo, Japan, ²Department of Functioning and Disability, Hokkaido University Faculty of Health Sciences, Sapporo, Japan, ³Siemens Healthcare K.K., Tokyo, Japan, ⁴Global Center for Biomedical Science and Engineering, Hokkaido University Faculty of Medicine, Sapporo, Japan

Keywords: Neurofluids, Brain, sleep, jet lag, glymphatic system, metabolite, cognition, functional connectivity

Little had been reported about the effect of nighttime awakening (virtual jet lag) on the brain structure and function. In this prospective study which evaluated if short-time nighttime awakening due to virtual conference attendance affected the brain function, increased sleepiness, impaired information-processing ability, decreased mALPS index to suggest impaired glymphatic system functioning, a trend toward altered functional connectivity, were observed after nighttime awakening. The finding on mALPS index was similar to true jet lag.